DARUNAVIR 400 mg Film-Coated Tablets

Зміст інструкції

1. Darunavir Krka d.d. 400 mg film-coated tablets, 800 mg film-coated tablets
   1. What is Darunavir Krka d.d. and what it is used for
   2. What you need to know before taking Darunavir Krka d.d.
   3. How to take Darunavir Krka d.d.
   4. Possible side effects
   5. How to store Darunavir Krka d.d.
   6. Package contents and other information
2. Darunavir Krka d.d. 600 mg film-coated tablets
   1. What is Darunavir Krka d.d. and what is it used for
   2. What you need to know before taking Darunavir Krka d.d.
   3. How to take Darunavir Krka d.d.
   4. Possible side effects
   5. How to store Darunavir Krka d.d.
   6. Package Contents and Other Information

Darunavir Krka d.d. 400 mg film-coated tablets, 800 mg film-coated tablets

darunavir

Read 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4. Contents of this leaflet:
• 1. What Darunavir Krka d.d. is and what it is used for
• 2. What you need to know before you take Darunavir Krka d.d.
• 3. How to take Darunavir Krka d.d.
• 4. Possible side effects
• 5. How to store Darunavir Krka d.d.
• 6. Contents of the pack and other information

1. What is Darunavir Krka d.d. and what it is used for

What is Darunavir Krka d.d.?
Darunavir Krka d.d. contains the active ingredient darunavir. Darunavir Krka d.d. is a
antiretroviral medicine, used in the treatment of human immunodeficiency virus (HIV) infection.
It belongs to a group of medicines called protease inhibitors. Darunavir Krka d.d. works by
reducing the amount of HIV in the body, improving the immune system and reducing the risk
of developing diseases related to HIV infection.

What is it used for?
Darunavir Krka d.d. 400 and 800 milligram tablets are used in the treatment of adults and
children (aged 3 years or older and weighing at least 40 kilograms) with
HIV infection

• who have not used other antiretroviral medicines before.
• in some patients who have already used antiretroviral medicines before (the doctor will determine who to administer it to) Darunavir Krka d.d. must be taken in combination with a low dose of cobicistat or ritonavir and with other anti-HIV medicines. The doctor will discuss with you the best combination of medicines for you.

2. What you need to know before taking Darunavir Krka d.d.

Do not take Darunavir Krka d.d.

• if you are allergicto the active substance, or to any of the other ingredients of this medicine (listed in section 6),
• if you have severe liver problems. Ask your doctor for advice if you are not sure about the severity of your liver disease. Further tests may be necessary. Do not combine Darunavir Krka d.d. with any of the following medicinesIf you are taking any of these medicines, ask your doctor how to switch to another medicine.

Do not combine Darunavir Krka d.d. with products containing St John's Wort ( Hypericum

perforatum).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Darunavir Krka d.d..
Darunavir Krka d.d. is not a cure for HIV infection. You may still transmit HIV while
taking this medicine, although the risk is reduced by the effect of antiretroviral therapy.
Discuss with your doctor the precautions necessary to avoid transmitting the infection to others.
People taking Darunavir Krka d.d. may also develop infections or other diseases
associated with HIV infection. You should stay in regular contact with your doctor.
Patients taking Darunavir Krka d.d. may develop a rash. Rarely
the rash may become severe or potentially life-threatening. Contact your doctor every
time you develop a rash.
In patients taking Darunavir Krka d.d. and raltegravir (for HIV infection), rashes
(usually mild or moderate) may occur more frequently than in patients taking
each medicine separately.

Inform your doctor about your condition BEFORE and DURING therapy
Make sure to check the following points and tell your doctor if any of these apply to you.

• Inform your doctor if you have had liver problemsin the past, including hepatitis B or C infection. The doctor can assess the severity of your liver disease before deciding whether to administer Darunavir Krka d.d.
• Inform your doctor if you have diabetes. Darunavir Krka d.d. may increase blood sugar levels.

blood.

• Immediately inform your doctor if you notice any signs of infection(e.g. swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to be due to an improvement in the body's immune response, which allows the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you have started taking medications to treat HIV infection. Autoimmune disorders can occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, initial weakness in hands and feet that rises towards the body trunk, palpitations, tremors or hyperactivity, immediately inform your doctor to request the necessary treatment.
• Inform your doctor if you have hemophilia. Darunavir Krka d.d. may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides(used to treat some infections).
• Inform your doctor if you notice any musculoskeletal problems. Some patients taking a combination of antiretroviral medications may develop a bone disease called osteonecrosis (bone tissue death caused by a lack of blood supply to the bone). Some of the many risk factors for developing this disease may be the duration of use of antiretrovirals in combination, the use of corticosteroids, alcohol consumption, severe immunodeficiency, a high body mass index. Signs of osteonecrosis are joint swelling, pain and aches (especially in the hip, knee and shoulders) and difficulty moving. If you notice any of these symptoms, immediately inform your doctor. ElderlyDarunavir Krka d.d. has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor before taking Darunavir Krka d.d.. Children and adolescentsDarunavir Krka d.d. 400 or 800 milligram tablets should not be used in children under 3 years of age or weighing less than 40 kilograms. Other medicines and Darunavir Krka d.d.Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. There are some medicines that must not be combinedwith Darunavir Krka d.d.. These have been listed previously under the heading “Do not combine Darunavir Krka d.d. with any of the following medicines”. In most cases, Darunavir Krka d.d. can be combined with anti-HIV medicines that belong to another class [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir Krka d.d. in combination with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and should not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always tell your doctor if you are taking other anti-HIV medicines and carefully follow your doctor's instructions on which medicines you can take. The effects of Darunavir Krka d.d. may be reduced if you take any of the following medicines. Tell your doctor if you take:
• Phenobarbital, phenytoin (to prevent epileptic seizures)
• Dexamethasone (a corticosteroid)
• Efavirenz (to treat HIV infection)
• Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)
• Saquinavir (to treat HIV infection).

The effects of other medicines may be affected by taking Darunavir Krka d.d..
Tell your doctor if you take:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide,lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil(for heart disease), as the therapeutic effect or side effects of these medicines may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin, clopidogrel(to reduce blood clotting), because both the therapeutic effect and side effects may be altered; your doctor may need to perform a blood test.
• Hormonal contraceptives based on estrogens or hormone replacement therapy. Darunavir Krka d.d. may reduce their effectiveness. When hormone therapy is used for contraceptive purposes, the use of other methods of contraception is recommended.
• Ethinylestradiol/drospirenone:Darunavir Krka d.d. may increase the risk of an increase in potassium levels due to drospirenone .
• Atorvastatin, pravastatin, rosuvastatin(to lower cholesterol levels). It may increase the risk of muscle damage. The doctor will assess which medicine to reduce cholesterol is most suitable for you.
• Clarithromycin(antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus(to reduce the activity of the immune system). Because the therapeutic effect or side effects of these medicines may be increased, the doctor may want to perform further tests.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone,triamcinolone.These medicines are used in the treatment of allergies, asthma, inflammatory bowel disease, skin, eye, joint and muscle inflammatory conditions and other types of inflammatory conditions. These medicines are generally taken orally, by inhalation, injection or applied to the skin. If alternative treatments cannot be used, these medicines can only be taken after evaluation by the doctor and under close monitoring by the doctor of the side effects due to corticosteroids .
• Buprenorphine/naloxone(to treat opioid dependence).
• Salmeterol(for the treatment of asthma).
• Artemether/lumefantrine(a combination of medicines for the treatment of malaria) .
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine(to treat cancer)
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or for the treatment of a heart or lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir(to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol(for the treatment and care of pain)
• Fesoterodine, solifenacin(to treat urological disorders). It may be necessary to adjust the dosage of other medicines because the therapeutic effect and side effects of these medicines or Darunavir Krka d.d. may be affected if combined. Tell your doctor if you take:
• Alfentanil(strong short-acting injectable pain reliever used for surgery)
• Digoxin(for the treatment of some heart disorders)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole can only be taken after evaluation by the doctor
• Rifabutin(against bacterial infections)
• Sildenafil, vardenafil, tadalafil(for erectile dysfunction or high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone(for the treatment of depression and anxiety)
• Maraviroc(to treat HIV infection)
• Methadone(to treat opioid dependence)
• Carbamazepine, clonazepam(to prevent seizures or to treat some types of neuropathic pain)
• Colchicine(to treat gout or familial Mediterranean fever)
• Bosentan(to treat high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when usedin injection form, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(to treat psychiatric conditions)
• Metformin(to treat type 2 diabetes). This is nota complete list of medicines. Tell your doctor about allthe medicines you are taking. Darunavir Krka d.d. with food and drinkSee section 3 “How to take Darunavir Krka d.d.” Pregnancy and breastfeedingImmediately inform your doctor if you are pregnant, planning a pregnancy or breastfeeding. Pregnant women or breastfeeding mothers should not take Darunavir Krka d.d. with ritonavir, unless they receive specific instructions from their doctor. Pregnant women or breastfeeding mothers should not take darunavir with cobicistat. It is recommended that women with HIV infection do not breastfeed infants, both for the possibility of transmitting HIV infection to children through breast milk, and for the unknown effects of Darunavir Krka d.d. on children. Driving and using machinesDo not use machinery or drive if you feel dizzy after taking Darunavir Krka d.d..

3. How to take Darunavir Krka d.d.

Take this medicine always exactly as your doctor, pharmacist or
nurse has told you. If you have doubts, ask your doctor, pharmacist or nurse.
Even if you feel better, do not stop taking Darunavir Krka d.d. and cobicistat or ritonavir
without talking to your doctor.
After therapy has been started, the dose or dosage form must not be changed or the
therapy must not be interrupted without instructions from your doctor.
Darunavir Krka d.d. 400 and 800 milligram tablets must be used only to build the 800 milligram once-daily
regimen.
This product is only available as film-coated tablets and is therefore not suitable for patients
who cannot swallow whole tablets, such as small children. For use in these
patients, the availability of more appropriate formulations containing darunavir must be verified.

Dose for adults who have not previously taken antiretroviral drugs (your doctor
will assess this)
The usual dose of Darunavir Krka d.d. is 800 milligrams (2 tablets containing 400 milligrams
of Darunavir Krka d.d. or 1 tablet containing 800 milligrams of Darunavir Krka d.d.) once daily.
You must take Darunavir Krka d.d. every day and always together with 150 milligrams of cobicistat or
100 milligrams of ritonavir and with food. Darunavir Krka d.d. may not work as well without
cobicistat or ritonavir and without food. You should have a meal or snack within 30 minutes before
taking Darunavir Krka d.d. and cobicistat or ritonavir. The type of food is irrelevant. Even if you
feel better, do not stop taking Darunavir Krka d.d. and cobicistat or ritonavir before talking
to your doctor.

Instructions for adults

• Take two 400 milligram tablets at the same time, once a day, every day
• Take Darunavir Krka d.d. always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir
• Take Darunavir Krka d.d. with food
• Swallow the tablets with a drink such as water or milk
• Take the other medicines for HIV used in combination with Darunavir Krka d.d. and cobicistat or ritonavir following your doctor’s instructions. Adults who have already taken antiretrovirals previously (your doctor will assess this)You will probably need a different dose of Darunavir Krka d.d. that cannot be administered with these 400 or 800 milligram tablets. Other dosages of Darunavir Krka d.d. are available. The dose is:
• 800 milligrams of Darunavir Krka d.d. (2 tablets containing 400 milligrams of Darunavir Krka d.d. or 1 tablet containing 800 milligrams of Darunavir Krka d.d.) together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily OR
• 600 milligrams of Darunavir Krka d.d. (1 tablet containing 600 milligrams of Darunavir Krka d.d.) together with 100 milligrams of ritonavir twice daily

Discuss with your doctor which is the most correct dose.

Dose for children aged 3 years and over with ritonavir and aged 12 years and over with cobicistat, and weighing more than 40 kilograms who have not previously taken antiretroviral medicines (the child’s doctor will determine this condition)

• The usual dose of Darunavir Krka d.d. is 800 milligrams once a day (2 tablets containing 400 milligrams of Darunavir Krka d.d. or 1 tablet containing 800 milligrams of Darunavir Krka d.d.) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily. Dose for children aged 3 years and over with ritonavir and aged 12 years and over with cobicistat, and weighing more than 40 kilograms who have previously taken antiretroviral medicines (the child’s doctor will determine this condition)The dose is both:
• 800 milligrams of Darunavir Krka d.d. (2 tablets containing 400 milligrams of Darunavir Krka d.d. or 1 tablet containing 800 milligrams of Darunavir Krka d.d.) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily. OR
• 600 milligrams of Darunavir Krka d.d. (1 tablet containing 600 milligrams of Darunavir Krka d.d.) together with 100 milligrams of ritonavir twice daily. Discuss with your doctor which is the most correct dose. Instructions for children aged 3 years and over with ritonavir and aged 12 years and over with cobicistat, weighing more than 40 kilograms
• Take 800 milligrams of Darunavir Krka d.d. (2 tablets containing 400 milligrams of Darunavir Krka d.d. or 1 tablet containing 800 milligrams of Darunavir Krka d.d.) at the same time, once a day, every day.
• Take Darunavir Krka d.d. always together with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
• Take Darunavir Krka d.d. with food.
• Swallow the tablets with a drink such as water or milk.
• Take the other medicines for HIV used in combination with Darunavir Krka d.d. and ritonavir or cobicistat as recommended by your doctor. If you take more Darunavir Krka d.d. than you should

Tell your doctor, pharmacist or nurse immediately.

If you forget to take Darunavir Krka d.d.
If you remember within 12 hours, you should take the tablets immediately. Always take the
tablets together with cobicistat or ritonavir and food. If you remember after 12 hours, skip the dose and
take the next dose as usual. Do not take a double dose to make up for a missed dose.

In case of vomiting after taking Darunavir Krka d.d. and cobicistat or ritonavir
If you vomit within 4 hoursof taking the medicine, you should take another dose of
Darunavir Krka d.d. and cobicistat or ritonavir with food as soon as possible. If vomiting occurs more
than 4 hoursafter taking the medicine, you do not need to take another dose of Darunavir
Krka d.d. and cobicistat or ritonavir until the time usually scheduled for the next dose.
Contact your doctor if you have any doubtsabout what to do if you forget a dose or vomit.

Do not stop treatment with Darunavir Krka d.d. without first consulting your doctor
Anti-HIV medicines can make you feel better. Do not stop taking Darunavir Krka d.d., even
if you feel better. Consult your doctor first.
If you have any questions about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

During HIV therapy, an increase in weight and levels of lipids and glucose in the blood may occur.
This is partly related to the restoration of health and lifestyle, and in the case of blood lipids, sometimes to the HIV medications themselves. The doctor will check these
changes.
Like all medicines, this medicine can cause side effects, although not everyone
will experience them.

Tell your doctor if you develop any of the following side effects
Liver problems have been reported that can occasionally be serious. The doctor will need to
perform blood tests before starting Darunavir Krka d.d.. If you have chronic hepatitis B or C, the
doctor should check your blood tests more frequently because you are more
likely to develop liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain,
soreness or tenderness on the right side under the ribs.
Skin rashes (more frequent when used in combination with raltegravir), itching. These rashes
are usually mild to moderate in grade. A rash can also be a symptom of a
more serious and rare condition. It is therefore important that you consult your doctor if you develop a
rash. The doctor will advise you on how to treat the symptoms or whether Darunavir Krka d.d. should be
discontinued.
Other serious side effects were diabetes (common) and pancreatitis (uncommon).
Very common side effects (may affect more than 1 in 10 people)

• diarrhea Common side effects (may affect up to 1 in 10 people)
• vomiting, nausea, abdominal pain or distension, dyspepsia (indigestion), flatulence
• headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in the hands or feet, loss of strength, difficulty falling asleep

Effects not common (may affect up to 1 in 100 people)

• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, balance problems
• difficulty breathing, cough, nosebleeds, sore throat
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• muscle pain, muscle cramps or weakness, pain in the extremities, osteoporosis
• slowing of thyroid function. This can be demonstrated by blood tests.
• high blood pressure, hot flushes
• red or dry eyes
• fever, leg swelling due to fluid retention, malaise, chills, abnormal sensations, irritability, pain
• infection symptoms, herpes simplex
• erectile dysfunction (problems with erection), breast enlargement
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire Uncommon side effects (may affect up to 1 in 1,000 people)
• a reaction called DRESS [severe rash that may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cells), effects on the liver, kidneys or lungs]
• heart attack, slow heartbeat, palpitations
• vision disorders
• chills, feeling unwell
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, seizures, change or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• runny nose
• skin lesions, dry skin
• muscle or joint stiffness, joint pain with or without inflammation
• changes in some blood cell or chemical values. These can be seen in blood and/or urine tests. The doctor will explain these results to you. Examples are: increased white blood cells. Some side effects are typical of anti-HIV medicines from the same family as Darunavir Krka d.d.. These are as follows:
• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe. Reporting of side effectsIf you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the reporting system indicated in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Darunavir Krka d.d.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and bottle after
EXP. The expiry date refers to the last day of that month.
Keep the bottle tightly closed to protect the medicine from moisture.
Validity after first opening: 3 months.
Do not dispose of any medicine in waste water or household waste. 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 Darunavir Krka d.d. contains

• The active ingredient is darunavir. Each tablet contains 400 mg or 800 mg of darunavir.
• The other ingredients are: microcrystalline cellulose, crospovidone, hydroxypropylcellulose, anhydrous colloidal silicon dioxide, silicified microcrystalline cellulose (microcrystalline cellulose; anhydrous colloidal silicon dioxide) and magnesium stearate (E470b) in the tablet core and poly(vinyl alcohol), macrogol, titanium dioxide (E171), talc (E553b) yellow iron oxide (E172) - only for the 400 mg film-coated tablets and red iron oxide (E172) in the tablet coating.

Description of the appearance of Darunavir Krka d.d. and package contents

Darunavir Krka d.d. 400 mg film-coated tablets (tablets):
Film-coated tablets (tablets), brownish-yellow, oval, biconvex, with an inscription
S1 on one side. Tablet size: 17 x 8.5 mm.

Darunavir Krka d.d. 800 mg film-coated tablets (tablets):
Film-coated tablets (tablets), reddish-brown, oval, biconvex, with an inscription
S3 on one side. Tablet size: 20 x 10 mm.
Darunavir Krka d.d. 400 mg film-coated tablets are available in bottles containing 30
film-coated tablets (1 bottle of 30 film-coated tablets), 60 film-coated tablets (2 bottles of 30
film-coated tablets), 90 film-coated tablets (3 bottles of 30 film-coated tablets) and 180 film-coated
tablets (6 bottles of 30 film-coated tablets) in a carton.
Darunavir Krka d.d. 800 mg film-coated tablets are available in bottles containing 30
film-coated tablets (1 bottle of 30 film-coated tablets) and 90 film-coated tablets
(3 bottles of 30 film-coated tablets) in a carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straβe 5, 27472 Cuxhaven, Germany
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: +32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

БългарияLuxembourg/Luxemburg
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50
KRKA Belgium, SA.
Tél/Tel: +32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta

• E. J. Busuttil Ltd. Tel: + 356 21 445 885 DeutschlandTAD Pharma GmbH Tel: + 49 (0) 4721 606-0 NederlandKRKA Belgium, SA. Tel: +32 (0) 487 50 73 62 (BE) EestiKRKA, d.d., Novo mesto Eesti filiaal Tel: + 372 (0) 6 671 658 NorgeKRKA Sverige AB Tlf: + 46 (0)8 643 67 66 (SE) ΕλλάδαKRKA ΕΛΛΑΣ ΕΠΕ Τηλ: +30 2100101613 ÖsterreichKRKA Pharma GmbH, Wien Tel: + 43 (0)1 66 24 300 EspañaKRKA Farmacéutica, S.L. Tel: + 34 911 61 03 80 PolskaKRKA-POLSKA Sp. z o.o. Tel.: + 48 (0)22 573 7500 FranceKRKA France Eurl Tél: + 33 (0)1 57 40 82 25 PortugalKRKA Farmacêutica, Sociedade Unipessoal Lda. Tel: + 351 (0)21 46 43 650 HrvatskaKRKA - FARMA d.o.o. Tel: + 385 1 6312 100 RomâniaKRKA Romania S.R.L., Bucharest Tel: + 4 021 310 66 05 IrelandKRKA Pharma Dublin, Ltd. Tel: + 353 1 413 3710 SlovenijaKRKA, d.d., Novo mesto Tel: + 386 (0) 1 47 51 100 ÍslandLYFIS ehf. Sími: +354 534 3500 Slovenská republikaKRKA Slovensko, s.r.o. Tel: + 421 (0) 2 571 04 501 ItaliaKRKA Farmaceutici Milano S.r.l. Tel: + 39 02 3300 8841 Suomi/FinlandKRKA Finland Oy Puh/Tel: +358 20 754 5330 ΚύπροςKI.PA. (PHARMACAL) LIMITEDΤηλ: + 357 24 651 882 SverigeKRKA Sverige AB Tel: + 46 (0)8 643 67 66 (SE) LatvijaKRKA Latvija SIA Tel: + 371 6 733 86 10 United Kingdom (Northern Ireland)Krka Pharma Dublin, Ltd. Tel: +353 1 413 3710

More detailed information on this medicinal product is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/ .

Darunavir Krka d.d. 600 mg film-coated tablets

darunavir

Read this leaflet carefully before you start taking this medicine as it contains important information for you.

• 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4. Contents of this leaflet:
• 1. What Darunavir Krka d.d. is and what it is used for
• 2. What you need to know before you take Darunavir Krka d.d.
• 3. How to take Darunavir Krka d.d.
• 4. Possible side effects
• 5. How to store Darunavir Krka d.d.
• 6. Contents of the pack and other information

1. What is Darunavir Krka d.d. and what is it used for

What is Darunavir Krka d.d.?
Darunavir Krka d.d. contains the active substance darunavir. Darunavir Krka d.d. is a medicine
antiretroviral, used in the treatment of human immunodeficiency virus (HIV) infection.
It belongs to a group of medicines called protease inhibitors. Darunavir Krka d.d. works
by reducing the amount of HIV in the body, improving the immune system and reducing the risk
of developing diseases related to HIV infection.

What is it used for?
Darunavir Krka d.d. is used for the treatment of adults and children aged 3 years or
older, and weighing at least 15 kilograms, who are affected by HIV infection and who have already
used other antiretroviral medicines previously.
Darunavir Krka d.d. must be taken in association with a low dose of ritonavir and with other
anti-HIV medicines. The doctor will discuss with you the best combination of medicines for you.

2. What you need to know before taking Darunavir Krka d.d.

Do not take Darunavir Krka d.d.

• if you are allergicto the active ingredient, or to any of the other ingredients of this medicine (listed in section 6),
• if you have severe liver problems. Ask your doctor for advice if you are not sure about the severity of your liver disease. Further tests may be needed. Do not combine Darunavir Krka d.d. with any of the following medicinesIf you are taking any of these medicines, ask your doctor how to switch to another medicine.

Do not combine Darunavir Krka d.d. with products containing St. John's Wort ( Hypericum

perforatum).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Darunavir Krka d.d..
Darunavir Krka d.d. is not a cure for HIV infection. You may still transmit HIV while
taking this medicine, although the risk is reduced by the effect of antiretroviral therapy.
Discuss with your doctor the precautions necessary to avoid transmitting the infection to others.
People taking Darunavir Krka d.d. may also develop infections or other diseases
associated with HIV infection. You should stay in regular contact with your doctor.
Patients taking Darunavir Krka d.d. may develop a rash. Rarely
the rash may become severe or potentially life-threatening. Contact your doctor each
time you develop a rash.
In patients taking Darunavir Krka d.d. and raltegravir (for HIV infection), rashes
(generally mild or moderate) may occur more frequently than in patients taking
each medicine separately.

Inform your doctor about your condition BEFORE and DURING therapy
Make sure to check the following points and inform your doctor if any of these apply to you.

• Inform your doctor if you have had liver problemsin the past, including hepatitis B or C infection. Your doctor can assess the severity of your liver disease before deciding whether to administer Darunavir Krka d.d.
• Inform your doctor if you have diabetes. Darunavir Krka d.d. may increase blood sugar levels.
• Immediately inform your doctor if you notice any signs of infection(e.g. swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to be due to an improvement in the body's immune response, which allows the body to fight infections that may have been

present without causing obvious symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy tissue in the body) may also occur after you have started taking medicines to treat HIV infection. Autoimmune disorders can occur many months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet that rises towards the torso, palpitations, tremors or hyperactivity, immediately inform your doctor to request the necessary treatment.
• Inform your doctor if you have hemophilia. Darunavir Krka d.d. may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides(used to treat some infections).
• Inform your doctor if you notice any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (bone tissue death caused by a lack of blood supply to the bone). Some of the many risk factors for developing this disease include the duration of use of combination antiretrovirals, the use of corticosteroids, alcohol consumption, severe immunodeficiency, and a high body mass index. Signs of osteonecrosis are joint swelling, pain and aches (especially in the hip, knee and shoulder) and difficulty moving. If you notice any of these symptoms, immediately inform your doctor. ElderlyDarunavir Krka d.d. has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor before taking Darunavir Krka d.d. Children and adolescentsDarunavir Krka d.d. should not be used in children under 3 years of age or weighing less than 15 kilograms. Other medicines and Darunavir Krka d.d.Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. There are some medicines that must not be combinedwith Darunavir Krka d.d. These have been listed previously under the heading “Do not combine Darunavir Krka d.d. with any of the following medicines”. In most cases, Darunavir Krka d.d. can be combined with anti-HIV medicines that belong to another class [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir Krka d.d. in combination with ritonavir has not been studied with all PIs (protease inhibitors) and should not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor's instructions on which medicines you can take. The effects of Darunavir Krka d.d. may be reduced if you take any of the following medicines. Inform your doctor if you take:
• Phenobarbital, phenytoin(to prevent epileptic seizures)
• Dexamethasone(a corticosteroid)
• Efavirenz(to treat HIV infection)
• Rifapentine, rifabutin(medicines to treat some infections such as tuberculosis)
• Saquinavir(to treat HIV infection). The effects of other medicines may be affected by taking Darunavir Krka d.d. Inform your doctor if you take:
• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol,mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil(for heart disease),

because the therapeutic effect or side effects of these medicines may be
increased.

• Apixaban, edoxaban, rivaroxaban, warfarin, clopidogrel(to reduce blood clotting), because both the therapeutic effect and side effects may be altered; your doctor may need to perform a blood test.
• Hormonal contraceptives containing estrogen or hormone replacement therapy. Darunavir Krka d.d. may reduce their effectiveness. When hormone therapy is used for contraceptive purposes, the use of other contraceptive methods other than hormone therapy is recommended.
• Ethinylestradiol/drospirenone. Darunavir Krka d.d. may increase the risk of an increase in potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin(to lower cholesterol levels). It may increase the risk of muscle damage. Your doctor will assess which medicine to reduce cholesterol level is most suitable for you.
• Clarithromycin(antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus(to reduce the activity of the immune system). Because the therapeutic effect or side effects of these medicines may be increased, your doctor may want to perform further tests.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone,triamcinolone.These medicines are used in the treatment of allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint and muscle conditions and other types of inflammatory conditions. These medicines are generally taken orally, by inhalation, injection or applied to the skin. If alternative treatments cannot be used, these medicines can only be taken after assessment by the doctor and under close monitoring by the doctor for side effects due to corticosteroids .
• Buprenorphine/naloxone(to treat opioid dependence).
• Salmeterol(for the treatment of asthma).
• Artemeter/lumefantrine(a combination of medicines for the treatment of malaria) .
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine(to treat cancer)
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or for the treatment of a heart or lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir(to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol(for the treatment of pain).
• Fesoterodine, solifenacin(to treat urological disorders) .

It may be necessary to adjust the dosage of other medicines because the therapeutic effect and
side effects of these medicines or Darunavir Krka d.d. may be affected if
combined.
Tell your doctor if you are taking:

• Alfentanil(strong short-acting injectable pain reliever used for surgery)
• Digoxin(for the treatment of some heart disorders)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole can only be taken after assessment by the doctor
• Rifabutin(against bacterial infections)
• Sildenafil, vardenafil, tadalafil(for erectile dysfunction or for high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone(for the treatment of depression and anxiety)
• Maraviroc(to treat HIV infection)
• Methadone(to treat opioid dependence)
• Carbamazepine, clonazepam(to prevent epileptic seizures or to treat some types of neuropathic pain)
• Colchicine(to treat gout or familial Mediterranean fever)
• Bosentan(to treat high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used in the formof injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(to treat psychiatric conditions) This is nota complete list of medicines. Tell your doctor about allthe medicines you are taking. Darunavir Krka d.d. with food and drinkSee section 3 “How to take Darunavir Krka d.d.”. Pregnancy and breastfeedingImmediately inform your doctor if you are pregnant, planning a pregnancy or breastfeeding. Pregnant women or breastfeeding mothers should not take Darunavir Krka d.d. with ritonavir, unless they receive specific instructions from their doctor. Pregnant women or breastfeeding mothers should not take darunavir with cobicistat. It is recommended that women with HIV infection do not breastfeed infants, both for the possibility of transmitting HIV infection to children through breast milk, and for the unknown effects of Darunavir Krka d.d. on children. Driving and operating machineryDo not use machinery or drive if you experience dizziness after taking Darunavir Krka d.d.

3. How to take Darunavir Krka d.d.

Take this medicine always exactly as described in this leaflet or as instructed by your doctor, pharmacist or nurse. If you have any doubts, ask your doctor, pharmacist or nurse.
Even if you feel better, do not stop taking Darunavir Krka d.d. and ritonavir without talking to your doctor.
After therapy has been started, the dose or dosage form must not be changed or the therapy interrupted without instructions from your doctor.
Darunavir Krka d.d. 600 mg film-coated tablets should not be chewed or crushed.
This dosage is not suitable for doses less than 600 mg. It is not possible to administer all paediatric dosages with this medicine. Darunavir tablets with other dosages and formulations are available.

Dose for adults who have not previously taken antiretroviral drugs (your doctor will assess this)
Different dosages of Darunavir Krka d.d. may be required that cannot be administered with these 600 mg tablets. Other formulations of Darunavir Krka d.d. are available.

Dose for adults who have previously taken antiretroviral drugs (your doctor will assess this)
The doses are:

• 600 milligrams of Darunavir Krka d.d. (1 tablet containing 600 milligrams of Darunavir Krka d.d.) together with 100 milligrams of ritonavir twice a day OR
• 800 milligrams of Darunavir Krka d.d. (2 tablets containing 400 milligrams of Darunavir Krka d.d. or 1 tablet containing 800 milligrams of Darunavir Krka d.d.) together with 100 milligrams of ritonavir once a day. The 400 milligram and 800 milligram tablets of Darunavir Krka d.d. must only be used to build the 800 milligram once-daily regimen. Discuss with your doctor which dose is most appropriate.

Instructions for adults

• Always take Darunavir Krka d.d. with ritonavir. Darunavir Krka d.d. does not work properly without ritonavir.
• In the morning, take 1 tablet of 600 milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir.
• In the evening, take 1 tablet of 600 milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir.
• Take Darunavir Krka d.d. with food. Darunavir Krka d.d. does not work properly without food. The type of food taken is not important.
• Swallow the tablets with a drink such as water or milk. Dose for children aged 3 years or older and weighing at least 15kilograms who have not previously taken antiretroviral medicines (your child’s doctor will determine this)The doctor will calculate the correct daily dose each time based on the child’s body weight (see table below). This dose must not exceed the recommended adult dose, which is 800 milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir once a day. Your doctor will tell you how many Darunavir Krka d.d. tablets your child should take.

Dose for children aged 3 years or older and weighing at least 15
kg (kilograms) who have previously taken antiretroviral medicines (your child’s doctor will determine this)
The doctor will calculate the appropriate dose based on the child’s weight (see the table below). The
doctor will determine whether the once-daily or twice-daily dose is appropriate for the child. This dose must not exceed that recommended for adults, which corresponds to 600
milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir twice a day or 800
milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir once a day. The
doctor will tell you how many Darunavir Krka d.d. tablets and how much ritonavir (capsules,
tablets or solution) your child should take. Lower dosage tablets are available
and your doctor may have prescribed a specific combination of tablets to achieve the
appropriate dosing schedule.
The doctor will determine whether Darunavir Krka d.d. tablets are correct for the child.
Twice-daily dose
*
Once-daily dose

Instructions for children

• The child must take Darunavir Krka d.d. together with ritonavir. Darunavir Krka d.d. cannot work effectively without ritonavir.
• The child must take the appropriate doses of Darunavir Krka d.d. and ritonavir twice a day or once a day. If Darunavir Krka d.d. is prescribed twice a day, the child must take one dose in the morning and one dose in the evening. The doctor will determine which regimen is most appropriate for the child.
• The child must take Darunavir Krka d.d. with food. Darunavir Krka d.d. cannot work effectively without food. The type of food is not important.
• The child must swallow the tablets with a drink such as water or milk. If you take more Darunavir Krka d.d. than you shouldImmediately inform your doctor, pharmacist or nurse. If you forget to take Darunavir Krka d.d.If you realise within 6 hours, you should take the tablets immediately. Always take the tablets with ritonavir and food. If you realise after 6 hours, skip the dose and take the next dose as usual. Do not take a double dose to make up for a forgotten dose. If you vomit after taking Darunavir Krka d.d. and ritonavirIf you vomit within 4 hoursof taking the medicine, you should take another dose of Darunavir Krka d.d. and ritonavir with food as soon as possible. If vomiting occurs more than 4 hoursafter taking the medicine, you do not need to take another dose of Darunavir Krka d.d. and ritonavir until the time usually scheduled for the next dose. Contact your doctor if you have any doubtsabout what to do if you forget a dose or vomit. Do not stop treatment with Darunavir Krka d.d. without first consulting your doctorHIV medicines can make you feel better. Do not stop taking Darunavir Krka d.d., even if you feel better. Speak to your doctor first. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

During HIV therapy, an increase in weight and levels of lipids and glucose in the blood may occur.
This is partly related to the restoration of health and lifestyle, and in the case of blood lipids, sometimes to the
HIV medications themselves. The doctor will check these changes.
Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Tell your doctor if you develop any of the following side effects
Liver problems have been reported that can occasionally be serious. The doctor will need to perform blood
tests before starting Darunavir Krka d.d.. If you have chronic hepatitis B or C, the doctor should check your
blood tests more frequently because you are more likely to develop liver problems. Talk to your doctor about the
signs and symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark urine
(tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness or
discomfort on the right side under the ribs.
Skin rashes (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to
moderate in grade. A rash can also be a symptom of a more serious and rare condition. It is therefore important
that you consult your doctor if you develop a rash. The doctor will advise you on how to treat the symptoms or
whether Darunavir Krka d.d. should be discontinued.
Other serious side effects were diabetes (common) and pancreatitis (uncommon).
Very common side effects (may affect more than 1 in 10 people)

• diarrhoea Common side effects (may affect up to 1 in 10 people)
• vomiting, nausea, abdominal pain or distension, dyspepsia (indigestion), flatulence
• headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in the hands or feet, loss of strength, difficulty falling asleep Uncommon side effects (may affect up to 1 in 100 people)
• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensation, tingling sensation, attention disorders, memory loss, difficulty with balance
• difficulty breathing, cough, nosebleeds, throat irritation
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• muscle pain, muscle cramps or weakness, pain in the extremities, osteoporosis
• slowdown of thyroid function. This can be demonstrated through a blood test.
• high blood pressure, hot flushes
• red or dry eyes
• fever, leg swelling due to fluid retention, malaise, chills, abnormal sensations, irritability, pain
• infection symptoms, herpes simplex
• erectile dysfunction (problems with erection), breast enlargement
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire Rare side effects (may affect up to 1 in 1,000 people)
• a reaction called DRESS [severe rash that may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell), effects on the liver, kidneys or lungs]
• heart attack, slow heartbeat, palpitations
• visual disturbances
• chills, feeling unwell
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, seizures, change or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• runny nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in some blood cell or chemical values. These can be seen in blood and/or urine tests. The doctor will explain these results to you. Examples are: increased white blood cells. Some side effects are typical of anti-HIV medicines from the same family as Darunavir Krka d.d.. These are as follows:
• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also
report side effects directly through the reporting system detailed in Annex V.
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Darunavir Krka d.d.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and the bottle after
EXP. The expiry date refers to the last day of that month.
Keep the bottle tightly closed to protect the medicine from moisture.
Validity after first opening: 3 months.
Do not dispose of any medicine in waste water or household waste. 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 Darunavir Krka d.d. contains

• The active ingredient is darunavir. Each film-coated tablet contains 600 mg of darunavir.
• The other ingredients are microcrystalline cellulose, crospovidone, hydroxypropylcellulose, colloidal anhydrous silica, silicified microcrystalline cellulose (cellulose, microcrystalline; colloidal anhydrous silica), magnesium stearate (E470b) in the tablet core and poly(vinyl alcohol), macrogol, titanium dioxide (E171), talc (E553b), yellow iron oxide (E172) and red iron oxide (E172) in the tablet coating. Description of the appearance of Darunavir Krka d.d. and package contentsFilm-coated tablets (tablets) are brownish-orange, oval, biconvex, with an S2 mark on one side. Tablet size: 19.5 x 10 mm. Darunavir Krka d.d. is available in bottles containing 30 film-coated tablets (1 bottle of 30 film-coated tablets), 60 film-coated tablets (2 bottles of 30 film-coated tablets), 90 film-coated tablets (3 bottles of 30 film-coated tablets) and 180 film-coated tablets (6 bottles of 30 film-coated tablets) in a carton. Not all pack sizes may be marketed. Marketing Authorisation HolderKRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia ManufacturerKRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia TAD Pharma GmbH, Heinz-Lohmann-Straβe 5, 27472 Cuxhaven, Germany For further information on this medicine, contact the local representative of the marketing authorisation holder: België/Belgique/BelgienKRKA Belgium, SA. Tél/Tel: +32 (0) 487 50 73 62 LietuvaUAB KRKA Lietuva Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: +32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 36 (1) 355 8490

Danmark
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Malta

• E. J. Busuttil Ltd. Tel: + 356 21 445 885 DeutschlandTAD Pharma GmbH Tel: + 49 (0) 4721 606-0 NederlandKRKA Belgium, SA. Tel: +32 (0) 487 50 73 62 (BE) EestiKRKA, d.d., Novo mesto Eesti filiaal Tel: + 372 (0) 6 671 658 NorgeKRKA Sverige AB Tlf: + 46 (0)8 643 67 66 (SE) ΕλλάδαKRKA ΕΛΛΑΣ ΕΠΕ Τηλ: +30 2100101613 ÖsterreichKRKA Pharma GmbH, Wien Tel: + 43 (0)1 66 24 300 EspañaKRKA Farmacéutica, S.L. Tel: + 34 911 61 03 80 PolskaKRKA-POLSKA Sp. z o.o. Tel.: + 48 (0)22 573 7500 FranceKRKA France Eurl Tél: + 33 (0)1 57 40 82 25 PortugalKRKA Farmacêutica, Sociedade Unipessoal Lda. Tel: + 351 (0)21 46 43 650 HrvatskaKRKA - FARMA d.o.o. Tel: + 385 1 6312 100 RomâniaKRKA Romania S.R.L., Bucharest Tel: + 4 021 310 66 05 IrelandKRKA Pharma Dublin, Ltd. Tel: + 353 1 413 3710 SlovenijaKRKA, d.d., Novo mesto Tel: + 386 (0) 1 47 51 100 ÍslandLYFIS ehf. Sími: +354 534 3500 Slovenská republikaKRKA Slovensko, s.r.o. Tel: + 421 (0) 2 571 04 501 ItaliaKRKA Farmaceutici Milano S.r.l. Tel: + 39 02 3300 8841 Suomi/FinlandKRKA Finland Oy Puh/Tel: +358 20 754 5330 ΚύπροςKI.PA. (PHARMACAL) LIMITED Τηλ: + 357 24 651 882 SverigeKRKA Sverige AB Tel: + 46 (0)8 643 67 66 (SE) LatvijaKRKA Latvija SIA Tel: + 371 6 733 86 10 United Kingdom (Northern Ireland)Krka Pharma Dublin, Ltd. Tel: +353 1 413 3710

More detailed information on this medicine is available on the website of the European Medicines Agency, http://www.ema.europa.eu/