Norvir

Patient Information Leaflet: Information for the User

Norvir 100 mg powder for oral suspension

ritonavir
Please read all of this leaflet carefully before 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Norvir is and what it is used for
2. What you need to know before you or your child take Norvir
3. How to take Norvir
4. Possible side effects
5. How to store Norvir
6. Contents of the pack and other information

1. What Norvir is and what it is used for

Norvir contains the active substance ritonavir. Norvir is a protease inhibitor used in combination with other anti-HIV medicines (antiretrovirals) as a pharmacokinetic enhancer to control HIV infection. When used as an enhancer, Norvir does not treat HIV directly, but increases the levels of other protease inhibitors in the blood to improve their effect in controlling HIV infection.
Your doctor will discuss with you the optimal combination of medicines for your individual case.
Norvir is used in children from 2 years of age, adolescents and adults who have been infected with HIV.

2. What you should know before you or the child takes Norvir

Do not take Norvir

• if you are allergic to ritonavir or to any of the other ingredients of Norvir (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 allergic symptoms – these medicines may be purchased without a prescription);
• amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone, quinidine (used to correct irregular heartbeat);
• dihydroergotamine, ergotamine (used to treat migraine and headache);
• ergonovine, methylergonovine (used to stop excessive bleeding that may occur during childbirth or abortion);
• clorazepate, diazepam, estazolam, flurazepam, triazolam or oral midazolam (administered orally) (used to relieve sleep and/or anxiety disorders);
• 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]);
• meperidine, propoxyphene (used for pain relief);
• cisapride (used to relieve certain stomach problems);
• simvastatin, lovastatin (used to lower blood cholesterol levels);
• neratinib (used to treat breast cancer);
• lomitapide (used to lower blood cholesterol levels);
• alfuzosin (used to treat benign prostatic hyperplasia);
• fusidic acid (used to treat bacterial infections);
• sildenafil if you have a lung disease called pulmonary arterial hypertension causing breathing difficulties. Patients without this condition may use sildenafil for impotence (erectile dysfunction) under medical supervision (see section Other medicines and Norvir);
• avanafil or vardenafil (used to treat erectile dysfunction);
• colchicine (used to treat gout) if you have kidney or liver problems (see section Other medicines and Norvir);
• products containing St. John’s wort (Hypericum perforatum), which may reduce the effectiveness of Norvir. St. John’s wort is often found in herbal remedies that may be purchased without a prescription.

If you are currently taking any of these medicines, ask your doctor whether you can use an alternative medicine during treatment with Norvir.
Also read the list of medicines under “Other medicines and Norvir” regarding use with some of these medicines that require special care.

Warnings and precautions
Ask your doctor before taking Norvir.

Important information

• If Norvir is taken in combination with other antiretroviral medicines, it is important that you also read carefully the patient information leaflet provided with these medicines. These leaflets may contain additional information about situations in which Norvir should be avoided. If you have any further questions about Norvir (ritonavir) or other medicines prescribed to you, ask your doctor or pharmacist.
• Norvir is not a cure for HIV infection or AIDS.
• People taking Norvir may still develop infections or other diseases associated with HIV or AIDS. It is therefore important that you remain under medical supervision while taking Norvir.

Inform your doctor if you have/have had:

• A history of liver disease.
• Hepatitis B or C and are receiving combination antiretroviral therapy, as you are at increased risk of serious, potentially life-threatening liver-related side effects. You may need more frequent blood tests to monitor liver function.
• Haemophilia, as increased episodes of bleeding have been reported in haemophilia patients receiving this type of medicine (protease inhibitors). The reason for this is not yet known. You may require a higher dose of factor VIII to control bleeding episodes.
• Erectile dysfunction, as medicines used to treat erectile dysfunction may cause low blood pressure and prolonged erection.
• Diabetes, as worsening or onset of diabetes (diabetes mellitus) has been reported in some patients receiving protease inhibitors.
• Kidney disease, as your doctor may need to adjust the dose of other medicines (such as protease inhibitors).

Inform your doctor if you experience:

• Diarrhoea or vomiting that do not improve (persistent), as this condition may reduce the effectiveness of the medicines you are taking.
• Feeling unwell (nausea), vomiting or stomach pain, as these may be signs of inflammation of the pancreas (pancreatitis). Some patients taking Norvir may develop serious problems affecting the pancreas. If these symptoms occur, inform your doctor as soon as possible.
• Signs of infection – inform your doctor immediately. In some patients with advanced HIV infection (AIDS), shortly after starting anti-HIV treatment, signs and symptoms of previously acquired infections may appear, even if previously unknown. These symptoms are believed to result from improved immune response, enabling the body to fight such infections. In addition to opportunistic infections, autoimmune diseases (a condition in which the immune system attacks healthy body tissues) may also occur after starting HIV treatment. Autoimmune diseases may manifest several months after treatment initiation. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet spreading towards the trunk, palpitations, tremor or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Stiffness and joint pain (especially in the hip, knee and shoulder) and difficulty moving, inform your doctor, as this may be a symptom of a condition that can destroy bone tissue (osteonecrosis). Some patients taking certain types and combinations of antiretroviral medicines may develop this condition.
• Muscle pain, tenderness or weakness, particularly when associated with antiretroviral therapy including protease inhibitors and nucleoside analogues. In rare cases, these muscle disorders have been severe (see section 4 Possible side effects).
• Dizziness, feeling of emptiness in the head, fainting or abnormal heartbeat. Some patients taking Norvir may experience changes in the electrocardiogram (ECG). Inform your doctor if you have a heart condition or conduction disorder.
• If you have any other health concerns, discuss them with your doctor as soon as possible.

Children and adolescents
Norvir is not recommended for children under 2 years of age.

Other medicines and Norvir
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those without a prescription. There are some medicines that must not be taken with Norvir. These are listed above in section 2 under “Do not take Norvir”. There are some medicines that may be used only under certain circumstances as described below.
The following precautions may apply when Norvir is used as a pharmacokinetic enhancer with other medicines.
Inform your doctor if you are taking any of the medicines listed below, as special attention is required.

• Sildenafil or tadalafil for impotence (erectile dysfunction). The dose of these medicines must be reduced to avoid low blood pressure and prolonged erection. You must not take Norvir with sildenafil if you also have pulmonary arterial hypertension (see also section 2. What you should know before you or the child takes Norvir). Inform your doctor if you are taking tadalafil for pulmonary arterial hypertension.
• Colchicine (for gout), as Norvir may increase the levels of this medicine in the blood. You must not take Norvir with colchicine if you have kidney or liver problems (see also ‘Do not take Norvir’ above).
• Digoxin (a heart medicine). Your doctor may need to adjust the digoxin dose and monitor you while taking digoxin and Norvir to avoid heart problems.
• Hormonal contraceptives containing ethinylestradiol, as Norvir may reduce the effectiveness of these medicines. Use of condoms or other non-hormonal contraceptive methods is recommended. If you take this type of hormonal contraceptive with Norvir, you may experience irregular uterine bleeding (spotting).
• Atorvastatin or rosuvastatin (for high cholesterol). Norvir may increase the levels of these medicines in the blood. Ask your doctor before taking any cholesterol-lowering medicine with Norvir (see also “Do not take Norvir” above).
• Steroids (e.g. dexamethasone, fluticasone propionate, prednisolone, triamcinolone), as Norvir may increase the levels of these medicines in the blood, potentially leading to Cushing’s syndrome (round face) and reduced cortisol hormone production. Your doctor may decide to reduce the steroid dose or monitor side effects more closely.
• Trazodone (for depression). Undesirable effects such as nausea, dizziness, low blood pressure and weakness may occur when administered with Norvir.
• Rifampicin (for tuberculosis), as it may cause severe liver damage when taken with Norvir.
• Bosentan, riociguat (used for pulmonary arterial hypertension), as Norvir may increase the levels of these medicines in the blood.

There are other medicines that must not be taken with Norvir because their effects may increase or decrease when taken together. In some cases, your doctor may need to perform tests, adjust doses or monitor your condition regularly. Inform your doctor if you are taking any other medicine, whether prescribed or not, including herbal products, but it is particularly important to mention the following:

• amphetamine or amphetamine derivatives;
• antibiotics (e.g. erythromycin, clarithromycin, rifabutin);
• anticancer medicines (e.g. abemaciclib, afatinib, apalutamide, ceritinib, encorafenib, dasatinib, ibrutinib, nilotinib, venetoclax, vincristine, vinblastine);
• medicines used to treat low platelet count (e.g. fostamatinib);
• anticoagulants (e.g. dabigatran etexilate, edoxaban, rivaroxaban, vorapaxar, warfarin);
• antidepressants (e.g. amitriptyline, desipramine, fluoxetine, imipramine, nefazodone, nortriptyline, paroxetine, sertraline, trazodone);
• antifungals (e.g. ketoconazole, itraconazole, voriconazole);
• antihistamines (e.g. loratadine, fexofenadine);
• antiretrovirals including HIV protease inhibitors (atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, tipranavir), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and others (maraviroc, raltegravir);
• anti-tuberculosis medicines (bedaquiline and delamanid);
• antivirals used to treat chronic hepatitis C virus (HCV) infection in adults (e.g. glecaprevir/pibrentasvir and simeprevir);
• anxiolytics, buspirone;
• asthma medicines, theophylline, salmeterol;
• atovaquone, a medicine used to treat certain types of pneumonia and malaria;
• buprenorphine, a medicine used to treat chronic pain;
• bupropion, a medicine used to help stop smoking;
• antiepileptics (e.g. carbamazepine, valproate, lamotrigine, phenytoin);
• heart medicines (e.g. disopyramide, mexiletine, and calcium channel blockers such as amlodipine, diltiazem and nifedipine);
• medicines acting on the immune system (e.g. cyclosporine, tacrolimus, everolimus);
• levothyroxine (used to treat thyroid problems);
• morphine and morphine-like medicines used to treat severe pain (e.g. methadone, fentanyl);
• oral sedatives (e.g. alprazolam, zolpidem) and also injectable midazolam;
• tranquillisers (e.g. haloperidol, risperidone, thioridazine);
• colchicine, a medicine used to treat gout.

Some medicines must not be taken with Norvir under any circumstances. These are briefly listed in section 2 under “Do not take Norvir”.

Norvir with food and drink
See section 3.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, it is very important
to consult your doctor before taking this medicine.
There is substantial information on the use of ritonavir (active substance in Norvir) during pregnancy. In general, pregnant women have taken Norvir as a pharmacokinetic enhancer after the first three months of pregnancy in combination with other protease inhibitors. There is no evidence that Norvir increases the risk of birth defects compared to the general population.

Breastfeeding is not recommended for women living with HIV, as the virus may be transmitted to the infant through breast milk.
If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.

Driving or operating machinery
Norvir may cause dizziness. If this occurs, do not drive or operate machinery.

3. How to take Norvir

Take this medicine exactly as prescribed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist. Take this medicine once or twice daily every day with food.

For doses requiring exactly 100 mg (100 or 200 mg), pour the entire contents of each sachet onto soft food (such as applesauce or vanilla pudding) or mix with a small amount of liquid (water, chocolate milk, or infant formula), and consume the entire portion.

For doses less than 100 mg or for doses between amounts equal to 100 mg, the entire contents of the sachet must be mixed with liquid and then dosed using the appropriate volume in mL as directed by your doctor, using the oral dosing syringe.

For administration through a feeding tube, follow the instructions provided in the section “How do I take the correct dose of Norvir oral powder suspension mixed with liquids?”.

Use water to mix the medicine and follow the feeding tube instructions to administer the medicine.

The recommended dose of Norvir is:

Norvir is used to boost the effects of certain anti-HIV medicines. The specific adult dose is 1 or 2 sachets once or twice daily. For more detailed dosing recommendations, including those for children, refer to the package leaflet of the anti-HIV medicines with which Norvir is being co-administered.

Your doctor will inform you of the correct dose to take.

Norvir must be taken every day to help control HIV infection, regardless of how you feel. If a side effect prevents you from taking Norvir as prescribed, inform your doctor immediately. In cases of diarrhoea, your doctor may decide whether additional monitoring is needed.

Ensure you always have an adequate supply of medicine so you do not run out. When travelling or during hospital stays, make sure you have enough Norvir until you can obtain more.

Norvir oral suspension powder has a prolonged aftertaste. Eating peanut butter, hazelnut chocolate spread, or blackcurrant syrup immediately after taking the medicine may help eliminate the aftertaste.

Prepare only one dose at a time, using the correct number of sachets. Once the powder is mixed with food or liquid, make sure to take the entire dose within 2 hours. Do not mix Norvir with any other liquid without first consulting your doctor or pharmacist.

How do I take the correct dose of Norvir oral suspension powder mixed with food (entire sachet)?

Follow the instructions below:

Step 1. Before mixing the Norvir dose, gather the following supplies: (see Figure 1).

Step 2. Check your prescription for the number of sachets or contact your doctor or pharmacist.

Figure 1

Step 3. Before first use, wash the dosing cup for mixing with warm water and dish soap. Rinse and allow to air dry.

Step 4. Pour a small amount of soft food (applesauce or vanilla pudding) into the dosing cup (see Figure 2).

Figure 2

Step 5. Open the sachet (see Figure 3).

Figure 3

Step 6. Pour ALL the powder from the sachet into the food (see Figure 4).

Figure 4

Step 7. Mix thoroughly (see Figure 5).

Figure 5

Step 8. Administer the portion to the patient.

Step 9. The ENTIRE portion must be consumed (see Figure 6). If residual powder remains, add additional spoonfuls of food and administer to the patient. Use within 2 hours.

Figure 6

Step 10. Dispose of the empty sachet in the trash. Clean and dry the preparation area. Immediately wash the spoon and dosing cup with warm water and dish soap (see Figure 7). Rinse and allow to air dry.

Figure 7

How do I take the correct dose of Norvir oral suspension powder mixed with liquids?

Follow the instructions below:

What you need

Before mixing a dose of Norvir, gather the items shown in Figure 1. You may need more than one sachet per dose. Check the prescription instructions on the packaging or, if in doubt, call your doctor or pharmacist. If more than one sachet is needed, repeat all steps for each sachet.

Figure 1

Using the syringe

Before first use, wash the dosing syringe with warm water and dish soap. Rinse and allow to air dry.

Reading the scale

a. Each millilitre (mL) is marked as a number with a long line.
b. Each 0.2 mL is marked as a shorter line between the numbers.

Check the syringe before each use

You must use a new syringe if:

• you cannot clean the syringe
• you cannot read the scale
• you cannot move the plunger
• the syringe is damaged or leaking.

Step 1. Fill the syringe

a. Fully push the plunger into the syringe.
b. Insert the tip of the syringe into the liquid.
c. Slowly pull the plunger up to the 10 mL mark on the syringe (see Figure 2).

Figure 2

Step 2. Move any air bubbles to the tip of the syringe

a. Hold the syringe with the tip pointing upward.
b. Tap the syringe gently with the fingers of your other hand. This will move any air bubbles toward the tip.
c. Pull the plunger slightly downward. Be careful not to pull the plunger out of the syringe.
d. Tap the syringe again. This will help remove air bubbles and move them all to the tip (see Figure 3).

Figure 3

Step 3. Measure the liquid

a. Hold the syringe upright.
b. Slowly push the plunger upward until the top of the plunger reaches the 9.4 mL mark – this removes any air bubbles from the syringe (see Figure 4).

Figure 4

Step 4. Empty the syringe

a. Slowly push the plunger to empty the liquid from the syringe into the mixing dosing cup (see Figure 5).

Figure 5

Step 5. Pour the powder into the dosing cup

a. Open the sachet.
b. Pour all the powder into the dosing cup.
c. Check that the sachet is empty.

Be careful not to spill the powder outside the mixing dosing cup (see Figure 6).

Figure 6

Step 6. Mix the powder and liquid

a. Securely screw on the cap and shake the mixing dosing cup vigorously for at least 90 seconds until all lumps disappear.
b. Check for any remaining powder lumps. If lumps are still present, continue shaking until they disappear.
c. The liquid may appear cloudy – this is normal.
d. Let the liquid stand for 10 minutes and most bubbles will disappear.
e. You may notice small bubbles on the surface of the liquid – this is also normal (see Figure 7).

Figure 7

Step 7. Fill the syringe

a. Fully push the plunger into the syringe.
b. Place the tip of the syringe at the bottom of the mixing dosing cup.
c. Slowly pull the plunger to the 10 mL mark – try not to draw in any bubbles (see Figure 8).

Figure 8

Step 8. Remove all air bubbles

a. Hold the syringe with the tip pointing upward.
b. Tap the syringe gently with the fingers of your other hand to move air bubbles to the tip.
c. Push the plunger down slightly. Be careful not to push the plunger out of the syringe.
d. Tap the syringe again to remove air bubbles and move them all to the tip (see Figure 9).
e. Slowly push the plunger until a small amount of liquid appears at the tip of the syringe.
f. If large air bubbles remain, empty the liquid back into the mixing dosing cup and restart from Step 7.

Figure 9

Step 9. Measure the dose

a. Check the prescription instructions on the packaging for the dose in mL. If in doubt, call your doctor or pharmacist.
b. Insert the syringe tip into the mixing dosing cup and slowly push the plunger to the correct mL mark for the dose (see Figure 10).
c. If too much liquid is expelled, restart from Step 7. Be careful not to spill liquid from the mixing dosing cup.

Figure 10

Step 10. Administer the dose to the patient

a. Place the tip of the syringe inside the patient’s cheek.
b. Slowly push the plunger to administer the full dose (see Figure 11).
c. Give the patient the full dose within 2 hours of opening the sachet.

Figure 11

Step 11. (if needed)

If more than one sachet is required, repeat the entire procedure from the beginning.

Step 12. After you are finished

a. Dispose of the empty sachet and any remaining medicine in the mixing dosing cup into the waste bag.
b. Remove the plunger from the syringe.
c. Wash the syringe, plunger, mixing dosing cup, and cap by hand with warm water and dish soap. Rinse with water and allow to air dry. Do not wash these items in a dishwasher.
d. Clean and dry the area used for mixing the medicine.

If you take more Norvir than you should

If you take too much Norvir, you may experience numbness, tingling, or a prickling sensation.
If you realize you have taken more Norvir than prescribed, contact your doctor or the nearest hospital emergency department immediately.

If you forget to take Norvir

If you miss a dose, take it as soon as possible. If it is almost time for your next dose, take only that dose. Do not take a double dose to make up for the missed one.

If you stop taking Norvir

Even if you feel better, do not stop taking Norvir without talking to your doctor. Taking Norvir as prescribed gives you the best chance of delaying drug resistance.

4. Possible side effects

During therapy for HIV infection, an increase in weight and in blood lipid and glucose levels may occur. This is partly related to the recovery of health status and lifestyle, and, in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes.

Like all medicines, Norvir can cause side effects, although not everybody gets them. In addition, the side effects of Norvir used in combination with other antiretroviral medicines depend on these other medicines.

Therefore, it is important to carefully read the section on side effects included in the package leaflet of these medicines.

Very common: may affect more than 1 in 10 people

• Stomach ache (upper or lower)
• Vomiting
• Diarrhoea (can be severe)
• Feeling unwell (nausea)
• Flushing, feeling of warmth
• Headache
• Dizziness
• Sore throat
• Cough
• Stomach pain or indigestion
• Rash
• Joint pain and back pain
• Tingling or numbness
• Tingling or numbness in hands, feet, or around the lips and mouth
• Metallic taste in the mouth
• Feeling weak/tired
• Muscle weakness and pain

Common: may affect up to 1 in 10 people

• Allergic reactions including skin rash (skin may be red, raised, itchy), swelling of skin and other tissues
• Flatulence
• Loss of appetite
• Mouth ulcers
• Muscle pain, tenderness, or weakness
• Insomnia
• Anxiety
• Increased cholesterol
• Increased triglycerides
• Gout
• Stomach bleeding
• Liver inflammation and yellowing of the skin or whites of the eyes
• Increased frequency of urination
• Reduced kidney function
• Seizures
• Low platelet levels in blood
• Thirst (dehydration)
• Abnormally heavy menstrual period
• Cold hands and feet
• Acne
• Blood tests: changes in blood cell counts and chemical parameters
• Confusion
• Difficulty concentrating
• Fainting
• Blurred vision
• High blood pressure
• Low blood pressure and feeling faint when standing up

Uncommon: may affect up to 1 in 100 people

• Heart attack
• Kidney impairment
• Diabetes

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

• Severe reactions or those that may lead to death, including blistering skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Severe allergic reactions (anaphylaxis)
• High blood glucose levels

Not known: frequency cannot be estimated from available data

• Kidney stones

Tell your doctor if you experience nausea, vomiting, or stomach pain, as these may be symptoms of pancreatitis (inflammation of the pancreas). Also inform your doctor if you experience joint stiffness, tenderness, and pain (especially in the hips, knees, and shoulders), and difficulty moving, as these may be signs of osteonecrosis. See also section 2 What you need to know before you or your child take Norvir.

In patients with haemophilia A or B treated with this medicine or other protease inhibitors, an increased frequency of bleeding episodes (haemorrhage) has been reported. If this occurs, contact your doctor immediately.

Cases of diabetes mellitus or increased blood glucose levels have been reported in patients taking Norvir or other protease inhibitors.

Cases of impaired liver function, hepatitis, and rarely jaundice have been reported in patients treated with Norvir. Some of these patients had other medical conditions or were taking other medicines. Patients with pre-existing liver disease may experience worsening of their condition.

Muscle pain, tenderness, or weakness have been reported, particularly in patients taking lipid-lowering medicines (statins) in combination with antiretroviral therapy including protease inhibitors and nucleoside analogues. In rare cases, these muscle disorders have been severe (rhabdomyolysis). If you experience unexplained or persistent muscle pain, weakness, or fatigue, stop taking the medicine and contact your doctor as soon as possible or go to the nearest hospital or emergency department.

Contact your doctor immediately if, after taking Norvir, you notice symptoms that may indicate an allergic reaction, such as skin rash, itching, or difficulty breathing.

If any of the side effects becomes severe, or if you notice any side effects not listed in this leaflet, contact your doctor, pharmacist, emergency department, or seek immediate medical help in case of emergency.

Reporting of side effects

If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Norvir

Keep this medicine out of the sight and reach of children.
Do not use Norvir oral suspension powder after the expiry date stated on the sachet and on the
package. The expiry date refers to the last day of that month.
Norvir oral suspension powder must be stored at a temperature below 30°C.
Do not use this medicine if you notice that the powder is not beige/light yellow to yellow in colour.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines
you no longer use. This will help protect the environment.

6. Package contents and other information

What Norvir contains

• The active substance is ritonavir. Each sachet of Norvir contains 100 mg of ritonavir.
• The other components are copovidone; sorbitan laurate; anhydrous colloidal silica.

What Norvir looks like and contents of the pack
Norvir oral suspension powder is supplied in single sachets containing 100 mg of ritonavir.
30 sachets are packaged in a carton, which also contains 1 dosing cup for mixing and 2 oral dosing syringes.
It is possible that not all pack sizes are marketed.
Norvir is also supplied as film-coated tablets containing 100 mg of ritonavir.

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

Manufacturer
AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany
AbbVie Logistics B.V., Zuiderzeelaan 53, 8017 JV Zwolle, The Netherlands
AbbVie S.r.l., S.R. 148 Pontina km 52 SNC, 04011 Campoverde di Aprilia (LT), Italy

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

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.: +36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 9 1 384 0910 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0)1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel: +385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

More detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu/ .
To listen to or request a copy of this summary in , , or , please contact the local representative of the Marketing Authorisation Holder.

Package leaflet: information for the user

Norvir 100 mg film-coated tablets

ritonavir
Please read this leaflet carefully before taking this medicine because it contains
important information for you or the child.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Norvir is and what it is used for
2. What you need to know before you or the child take Norvir
3. How to take Norvir
4. Possible side effects
5. How to store Norvir
6. Contents of the pack and other information

1. What Norvir is and what it is used for

Norvir contains the active substance ritonavir. Norvir is a protease inhibitor used in combination with other anti-HIV medicines (antiretrovirals) as a pharmacokinetic enhancer to control HIV infection. Your doctor will discuss with you the optimal combination of medicines for your case. As an enhancer, Norvir does not treat HIV directly, but increases the levels of other protease inhibitors in the blood to improve their effect in controlling HIV infection.
Norvir is used in children aged 2 years and older, adolescents, and adults who have been infected with HIV.

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

Do not take Norvir

• if you are allergic to ritonavir or any of the other ingredients of Norvir (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 allergic symptoms – these medicines may be purchased without a prescription);
• amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone, quinidine (used to correct irregular heartbeat);
• dihydroergotamine, ergotamine (used to treat migraine and headache);
• ergonovine, methylergonovine (used to stop excessive bleeding that may occur during childbirth or abortion);
• clorazepate, diazepam, estazolam, flurazepam, triazolam or oral midazolam (administered orally) (used to relieve sleep and/or anxiety disorders);
• 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]);
• meperidine, propoxyphene (used for pain relief);
• cisapride (used to relieve certain stomach problems);
• simvastatin, lovastatin (used to lower cholesterol levels in the blood);
• neratinib (used to treat breast cancer);
• lomitapide (used to lower cholesterol levels in the blood);
• alfuzosin (used to treat benign prostatic hyperplasia);
• fusidic acid (used to treat bacterial infections);
• sildenafil if you suffer from a lung disease called pulmonary arterial hypertension causing breathing difficulties. Patients without this condition may use sildenafil for impotence (erectile dysfunction) under medical supervision (see section Other medicines and Norvir);
• avanafil or vardenafil (used to treat erectile dysfunction);
• colchicine (used to treat gout) if you have kidney or liver problems (see section Other medicines and Norvir);
• products containing St. John’s wort (Hypericum perforatum) as they may reduce the effectiveness of Norvir. St. John’s wort is often found in herbal remedies that may be purchased without a prescription.

If you are currently taking any of these medicines, ask your doctor whether you can use an alternative
medicine during treatment with Norvir.
Also read the list of medicines under “Other medicines and Norvir” regarding use with some of these
medicines which require special care.
Warnings and precautions
Talk to your doctor before taking Norvir.
Important information

• If Norvir is taken in combination with other antiretroviral medicines, it is important that you also read carefully the package leaflet provided with those medicines. Additional information about situations in which Norvir should be avoided may be included in those leaflets. If you have any further questions about Norvir (ritonavir) or other medicines prescribed to you, ask your doctor or pharmacist.
• Norvir is not a cure for HIV infection or AIDS.
• People taking Norvir may still develop infections or other diseases associated with HIV infection or AIDS. It is therefore important that you remain under medical supervision while taking Norvir.

Tell your doctor if you have/have had:

• A history of liver disease.
• Hepatitis B or C and are taking combination antiretroviral therapy, as you are at increased risk of serious, potentially life-threatening liver-related side effects. You may need more frequent blood tests to monitor liver function.
• Haemophilia, as increased episodes of bleeding have been reported in haemophiliac patients taking this type of medicine (protease inhibitors). The reason for this is not yet known. You may require a higher dose of factor VIII to control bleeding episodes.
• Erectile dysfunction, as medicines used to treat erectile dysfunction may cause low blood pressure and prolonged erection.
• Diabetes, as worsening or new-onset diabetes (diabetes mellitus) has been reported in some patients taking protease inhibitors.
• Kidney disease, as your doctor may need to adjust the dose of other medicines (such as protease inhibitors).

Tell your doctor if you experience:

• Diarrhoea or vomiting that does not improve (persistent), as this condition may reduce the effectiveness of your medicines.
• Feeling unwell (nausea), vomiting or stomach pain, as these may be signs of inflammation of the pancreas (pancreatitis). Some patients taking Norvir may develop serious problems affecting the pancreas. If you experience these symptoms, inform your doctor as soon as possible.
• Signs of infection – inform your doctor immediately. In some patients with advanced HIV infection (AIDS), shortly after starting anti-HIV treatment, signs and symptoms of past infections may appear, even though they were previously unaware of them. These symptoms are believed to result from improved immune response, allowing the body to fight such infections. In addition to opportunistic infections, autoimmune diseases (a condition in which the immune system attacks healthy body tissues) may also occur after starting HIV treatment. Autoimmune diseases may appear several months after treatment initiation. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in hands and feet and spreading towards the torso, palpitations, tremor or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Stiffness and pain in joints (especially hip, knee and shoulder) and difficulty moving, inform your doctor, as this may be a symptom of a condition that can destroy bone tissue (osteonecrosis). Some patients taking certain types and combinations of antiretroviral medicines may develop this condition.
• Muscle pain, tenderness or weakness, particularly when associated with antiretroviral therapy including protease inhibitors and nucleoside analogues. In rare cases, these muscle disorders have been severe (see section 4 Possible side effects).
• Dizziness, feeling of emptiness in the head, fainting or abnormal heartbeat. Some patients taking Norvir may experience changes in the electrocardiogram (ECG). Inform your doctor if you have a heart condition or conduction disorder.
• If you have any other concerns about your health, discuss them with your doctor as soon as possible.

Children and adolescents
Norvir is not recommended for children under 2 years of age.
Other medicines and Norvir
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those not requiring a prescription. There are some medicines that must not be taken with Norvir at all. These medicines are listed above in section 2 under “Do not take Norvir”. There are some medicines that may only be used under certain circumstances as described below.
The following precautions may apply when Norvir is used as a pharmacokinetic enhancer with other medicines.
Tell your doctor if you are taking any of the medicines listed below, as special attention is required in these cases.

• Sildenafil or tadalafil for impotence (erectile dysfunction). The dose of these medicines must be reduced to avoid low blood pressure and prolonged erection.

You must not take Norvir with sildenafil if you also have pulmonary arterial hypertension (see also section 2 What you need to know before you or the child takes Norvir). Inform your doctor if you are taking tadalafil for pulmonary arterial hypertension.

• Colchicine (for gout), as Norvir can increase the levels of this medicine in the blood. You must not take Norvir with colchicine if you have kidney or liver problems (see also ‘Do not take Norvir’ above).
• Digoxin (a heart medicine). Your doctor may need to adjust the digoxin dose and monitor you while taking digoxin and Norvir to prevent heart problems.
• Hormonal contraceptives containing ethinylestradiol, as Norvir may reduce the effectiveness of these medicines. Use of condoms or other non-hormonal contraceptive methods is recommended. If you take this type of hormonal contraceptive with Norvir, you may experience irregular uterine bleeding (spotting).
• Atorvastatin or rosuvastatin (for high cholesterol). Norvir can increase the levels of these medicines in the blood. Ask your doctor before taking any cholesterol-lowering medicine with Norvir (see also “Do not take Norvir” above).
• Steroids (e.g. dexamethasone, fluticasone propionate, prednisolone, triamcinolone), as Norvir can increase the levels of these medicines in the blood, potentially leading to Cushing’s syndrome (round face) and reduced cortisol hormone production. Your doctor may decide to reduce the steroid dose or monitor side effects more closely.
• Trazodone (for depression). When taken with Norvir, side effects such as nausea, dizziness, low blood pressure and weakness may occur.
• Rifampicin (for tuberculosis), as it may cause severe liver damage when taken with Norvir.
• Bosentan, riociguat (used for pulmonary arterial hypertension), as Norvir can increase the levels of these medicines in the blood.

There are other medicines that must not be taken with Norvir because their effects may increase or decrease when taken together. In some cases, your doctor may need to perform tests, adjust doses or monitor your condition regularly.
Inform your doctor if you are taking any other medicine, whether prescribed or not, including herbal products, but it is particularly important to mention the following:

• amphetamine or amphetamine derivatives;
• antibiotics (e.g. erythromycin, clarithromycin, rifabutin);
• anticancer medicines (e.g. abemaciclib, afatinib, apalutamide, ceritinib, encorafenib, dasatinib, ibrutinib, nilotinib, venetoclax, vincristine, vinblastine);
• medicines used to treat low platelet count in the blood (e.g. fostamatinib);
• anticoagulants (e.g. dabigatran etexilate, edoxaban, rivaroxaban, vorapaxar, warfarin);
• antidepressants (e.g. amitriptyline, desipramine, fluoxetine, imipramine, nefazodone, nortriptyline, paroxetine, sertraline, trazodone);
• antifungals (e.g. ketoconazole, itraconazole, voriconazole);
• antihistamines (e.g. loratadine, fexofenadine);
• antiretrovirals including HIV protease inhibitors (atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, tipranavir), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and others (maraviroc, raltegravir);
• anti-tuberculosis medicines (bedaquiline and delamanid);
• antivirals used to treat chronic hepatitis C virus (HCV) infection in adults (e.g. glecaprevir/pibrentasvir and simeprevir);
• anxiolytics, buspirone;
• asthma medicines, theophylline, salmeterol;
• atovaquone, a medicine used to treat certain types of pneumonia and malaria;
• buprenorphine, a medicine used to treat chronic pain;
• bupropion, a medicine used to help stop smoking;
• antiepileptics (e.g. carbamazepine, valproate, lamotrigine, phenytoin);
• heart medicines (e.g. disopyramide, mexiletine, and calcium channel blockers such as amlodine, diltiazem and nifedipine);
• medicines that act on the immune system (e.g. ciclosporin, tacrolimus, everolimus);
• levothyroxine (used to treat thyroid problems);
• morphine and morphine-like medicines used to treat severe pain (e.g. methadone, fentanyl);
• oral sedatives (e.g. alprazolam, zolpidem) and also injectable midazolam;
• tranquillisers (e.g. haloperidol, risperidone, thioridazine);
• colchicine, a medicine used to treat gout.

There are some medicines that must not be taken with Norvir under any circumstances. These are briefly listed in section 2 under “Do not take Norvir”.
Norvir with food and drink
Norvir tablets should be taken with food.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, it is very important that you consult your doctor before taking this medicine.
There is extensive information on the use of ritonavir (the active substance in Norvir) during pregnancy. In general, pregnant women have taken Norvir as a pharmacokinetic booster after the first three months of pregnancy in combination with other protease inhibitors. There is no evidence that Norvir increases the risk of birth defects compared to the general population.
Breastfeeding is not recommended for women living with HIV, as the virus can be transmitted to the infant through breast milk.
If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving or using machines
Norvir may cause dizziness. If this occurs, do not drive or operate machinery.
Norvir contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Norvir

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. This medicine must be taken once or twice daily, every day, with food.
It is important that Norvir tablets are swallowed whole and not chewed, divided, or crushed.

The recommended dose of Norvir is:

• Norvir is used to boost the effects of other anti-HIV medicines. The usual dosage for adults is 1 or 2 tablets once or twice daily. For more detailed dosing recommendations, including those for children, please refer to the Package Leaflet of the anti-HIV medicines used in combination with Norvir.

Your doctor will advise you on the correct dosage to take.
Norvir must be taken every day to help control HIV infection, regardless of how well you may feel. If a side effect makes it difficult for you to take Norvir as prescribed, inform your doctor immediately. In cases of diarrhoea, your doctor may decide whether further monitoring is needed.
Make sure you always have an adequate supply of medicine so that you do not run out. When travelling or during a hospital stay, ensure you have enough Norvir with you until you can obtain more.

If you take more Norvir than you should
If you take too much Norvir, you may experience dizziness, tingling, pricking, or stinging sensations. If you realize you have taken more Norvir than the correct dose, contact your doctor or the nearest hospital emergency department immediately.

If you forget to take Norvir
If you miss a dose of medicine, take it as soon as possible. If it is almost time for your next dose, take only that next dose. Do not take a double dose to make up for the missed dose.

If you stop taking Norvir
Even if you feel better, do not stop taking Norvir without first talking to your doctor. Taking Norvir as recommended gives you the best chance of delaying resistance to medicines.

4. Possible side effects

During therapy for HIV infection, an increase in weight, as well as in blood lipid and glucose levels, may occur. This is partly related to the recovery of health status and lifestyle, and, in the case of blood lipids, sometimes to the HIV medications themselves. Your doctor will monitor these changes.

Like all medicines, Norvir can cause side effects, although not everybody experiences them. In addition, the side effects of Norvir when taken with other antiretroviral medicines depend on these other medicines.

Therefore, it is important to read carefully the section on side effects in the package leaflet of these other medicines.

Very common: may affect more than 1 in 10 people

• stomach ache (upper or lower) • tingling or numbness sensation
• vomiting • weakness or fatigue
• diarrhoea (may be severe) • unpleasant taste in the mouth
• feeling unwell (nausea) • rash
• flushing, feeling of warmth • headache
• dizziness • joint pain and back pain
• sore throat • itching
• cough • nerve damage that may cause weakness and pain
• stomach pain or indigestion

Common: may affect up to 1 in 10 people

• allergic reactions including skin rash (skin may be red, raised, itchy), swelling of skin and other tissues • flatulence
• loss of appetite • mouth ulcers
• muscle pain, tenderness or weakness • insomnia
• anxiety • fever
• increased cholesterol • weight loss
• increased triglycerides • blood tests: changes in blood cell counts and chemical parameters
• gout • stomach bleeding
• liver inflammation and yellowing of the skin or whites of the eyes (jaundice) • difficulty concentrating
• increased frequency of urination • blurred vision
• reduced kidney function • swelling of hands and feet
• seizures • high blood pressure
• low platelet levels in blood • low blood pressure and feeling faint when standing up
• unusually heavy menstrual periods • coldness in hands and feet
• acne

Uncommon: may affect up to 1 in 100 people

• heart attack • kidney impairment
• diabetes

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

• severe reactions or those that may cause death, including blistering skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis) • severe allergic reactions (anaphylaxis) • high blood glucose levels

Not known: frequency cannot be estimated from the available data

• kidney stones

Tell your doctor if you experience feeling unwell (nausea), vomiting, or stomach pain, as these may be symptoms of pancreatitis. Also inform your doctor if you experience joint stiffness, tenderness, pain (especially in the hip, knee, or shoulder), or difficulty moving, as these may be signs of osteonecrosis. See also section 2. What you need to know before you or your child take Norvir.

Increased episodes of bleeding have been reported in patients with haemophilia A or B who are being treated with this medicine or other protease inhibitors. If this occurs, contact your doctor immediately.

Cases of impaired liver function, hepatitis, and rarely jaundice, have been reported in patients treated with Norvir. Some of these patients had other underlying diseases or were taking other medications. Patients with pre-existing liver disease may experience worsening of their condition.

Muscle pain, tenderness, or weakness have been reported in patients taking Norvir. This may be particularly observed when medicines to lower cholesterol are taken together with antiretroviral therapy including protease inhibitors and nucleoside analogues. In rare cases, these muscle disorders have been severe (rhabdomyolysis). If you experience persistent muscle pain, weakness, or fatigue, stop taking the medicine and contact your doctor immediately or go to the nearest hospital or emergency department.

Contact your doctor immediately if, after taking Norvir, you notice symptoms that may indicate an allergic reaction, such as skin rash, itching, or difficulty breathing.

If any of the side effects becomes severe, or if you notice any side effects not listed in this leaflet, contact your doctor, pharmacist, or go to the nearest emergency department. In case of emergency, seek immediate medical help.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Norvir

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature. Store in the original packaging to protect the medicine from moisture.
Do not use this medicine if you notice any changes in colour.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Norvir contains

• The active substance is ritonavir. Each film-coated tablet contains 100 mg of ritonavir.
• The other components of the tablet are: copovidone, sorbitan laurate, anhydrous dibasic calcium phosphate, anhydrous colloidal silica, sodium stearil fumarate.
• The tablet coating consists of: hypromellose, titanium dioxide, macrogol, hydroxypropylcellulose, talc, anhydrous colloidal silica, polysorbate 80.

Description of the appearance of Norvir and package contents
Norvir film-coated tablets are white, with the code “NK” imprinted on one side.
Norvir film-coated tablets are available in three pack sizes:

• 1 bottle containing 30 tablets
• 1 bottle containing 60 tablets
• Multiple pack: 3 bottles each containing 30 film-coated tablets (90 tablets total)

It is possible that not all pack sizes are marketed.
Norvir is also supplied as an oral suspension powder containing 100 mg of ritonavir.

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

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023

България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811

Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel.: +36 1 455 8600

Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 21220174

Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0

Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00

Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0

España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 9 1 384 0910 Tel.: +48 22 372 78 00

France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0)1 45 60 13 00 Tel: +351 (0)21 1908400

Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel: +385 (0)1 5625 501 Tel: +40 21 529 30 35

Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060

Ísland Slovenská republika
Vistor AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777

Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200

Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ: +357 22 34 74 40 Tel: +46 (0)8 684 44 600

Latvija
AbbVie SIA
Tel: +371 67605000

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/ .
To listen to or request a copy of this package leaflet in , or , please contact the local representative of the Marketing Authorisation Holder.