Darunavir Krka d.d.: detailed information

Package leaflet: Information for the patient

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

darunavir
Read this leaflet carefully before 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 give it to other people, even if they have the same symptoms as you, because it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact 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 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. Contents of the pack and other information

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

What Darunavir Krka d.d. is
Darunavir Krka d.d. contains the active substance darunavir. Darunavir Krka d.d. is an antiretroviral medicine used to treat 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 HIV-related illnesses.

What it is used for
Darunavir Krka d.d. 400 and 800 milligram tablets are used to treat adults and children (aged 3 years and older and weighing at least 40 kilograms) who are infected with HIV:

who have not previously used other antiretroviral medicines, or
in certain patients who have previously used antiretroviral medicines (your doctor will determine to whom it should be given).

Darunavir Krka d.d. must be taken in combination with a low dose of cobicistat or ritonavir and with other anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for your treatment.

2. What you should know before taking Darunavir Krka d.d.

Do not take Darunavir Krka d.d.

if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6),
if you have severe liver problems. Consult your doctor if you are unsure about the severity of your liver disease. You may need further tests. Do not take Darunavir Krka d.d. with any of the following medicines. If you are taking any of these medicines, ask your doctor how to switch to another medicine.

Medicine	Purpose of the medicine
Avanafil	for the treatment of erectile dysfunction
Astemizole or terfenadine	for the treatment of allergic symptoms
Triazolam and oral midazolam (taken by mouth)	used to help sleep and/or reduce anxiety
Cisapride	for the treatment of certain stomach disorders
Colchicine (if you have kidney and/or liver problems)	for the treatment of gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	for the treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	for the treatment of migraine
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	for the treatment of certain heart problems, for example, heart rhythm abnormalities
Lovastatin, simvastatin and lomitapide	to lower cholesterol levels
Rifampicin	for the treatment of certain infections, such as tuberculosis
Lopinavir/ritonavir combination	this anti-HIV medicine belongs to the same class as Darunavir Krka d.d.
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	to treat benign prostatic hyperplasia
Sildenafil	to treat high blood pressure in the pulmonary circulation
Dabigatran, ticagrelor	to help prevent platelet aggregation in the treatment of patients with a history of heart attack
Naloxegol	to treat opioid-induced constipation
Dapoxetine	to treat premature ejaculation
Domperidone	to treat nausea and vomiting

Do not co-administer 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 due to the effect of antiretroviral therapy. Discuss with your doctor the necessary precautions to avoid transmitting the infection to others.
People taking Darunavir Krka d.d. may still develop infections or other conditions associated with HIV infection. Regular follow-up with your doctor is essential.
Patients taking Darunavir Krka d.d. may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
Rashes (generally mild or moderate) may occur more frequently in patients taking Darunavir Krka d.d. and raltegravir (for HIV infection) together than in patients taking each medicine separately.
Inform your doctor about your medical condition BEFORE and DURING treatment
Please check the following points and inform your doctor if any of them apply to you.

Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe Darunavir Krka d.d.
Inform your doctor if you have diabetes. Darunavir Krka d.d. may increase blood sugar levels.
Inform your doctor immediately 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 infections, inflammatory signs and symptoms from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, allowing the body to fight infections that may have been present without causing obvious symptoms.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may appear several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
Inform your doctor if you have haemophilia. Darunavir Krka d.d. may increase the risk of bleeding.
Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Several risk factors for developing this condition include duration of combination antiretroviral therapy, use of corticosteroids, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint swelling, pain, and stiffness (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.
Elderly
Darunavir Krka d.d. has been administered to a limited number of patients aged 65 years and older. If you belong to this age group, consult your doctor before taking Darunavir Krka d.d.
Children and adolescents
Darunavir 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.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. There are certain medicines that must not be combined with Darunavir Krka d.d. These have already been listed earlier under the heading “Do not associate Darunavir Krka d.d. with any of the following medicines.” In most cases, Darunavir Krka d.d. can be combined with anti-HIV medicines belonging 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 must 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 regarding which medicines you may take. The effects of Darunavir Krka d.d. may be reduced if you take any of the following medicines. Inform your doctor if you are taking:
Phenobarbital, phenytoin (to prevent epileptic seizures)
Dexamethasone (a corticosteroid)
Efavirenz (to treat HIV infection)
Rifapentine, rifabutin (medicines to treat certain 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 are taking:

Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), 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 containing estrogens or hormone replacement therapy. Darunavir Krka d.d. may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
Ethinylestradiol/drospirenone: Darunavir Krka d.d. may increase the risk of elevated potassium levels due to drospirenone.
Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
Clarithromycin (antibiotic)
Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity). Since the therapeutic effect or side effects of these medicines may be increased, your doctor may wish to perform additional tests.
Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle disorders, and other inflammatory conditions. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under close medical monitoring for corticosteroid-related side effects.
Buprenorphine/naloxone (to treat opioid dependence)
Salmeterol (to treat asthma)
Artemether/lumefantrine (a combination of medicines to treat malaria)
Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)
Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension)
Glecaprevir/pibrentasvir (to treat hepatitis C infection)
Fentanyl, oxycodone, tramadol (for pain treatment)
Fesoterodine, solifenacin (to treat urological disorders)

Dosage adjustments of other medicines may be necessary because their therapeutic effects and side effects, or those of Darunavir Krka d.d., may be affected when used together. Inform your doctor if you are taking:

Alfentanil (a potent, short-acting injectable painkiller used during surgery)
Digoxin (to treat certain heart conditions)
Clarithromycin (antibiotic)
Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
Rifabutin (for bacterial infections)
Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for pulmonary hypertension)
Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
Maraviroc (to treat HIV infection)
Methadone (to treat opioid dependence)
Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
Colchicine (to treat gout or familial Mediterranean fever)
Bosentan (to treat high blood pressure in the lung circulation)
Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives)
Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)
Metformin (to treat type 2 diabetes)

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
Darunavir Krka d.d. with food and drinks
See section 3 “How to take Darunavir Krka d.d.”
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant women or breastfeeding mothers should not take Darunavir Krka d.d. with ritonavir unless specifically instructed by their doctor. Pregnant women or breastfeeding mothers should not take darunavir with cobicistat. Women with HIV infection are advised not to breastfeed their infants, both due to the risk of transmitting HIV infection through breast milk and due to unknown effects of Darunavir Krka d.d. on infants.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking Darunavir Krka d.d.

3. How to take Darunavir Krka d.d.

Take this medicine exactly as prescribed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Even if you feel better, do not stop taking Darunavir Krka d.d. and cobicistat or ritonavir without first talking to your doctor.
After treatment has been started, the dose or dosage form must not be changed, nor should treatment be discontinued, without instructions from your doctor.
Darunavir Krka d.d. 400 and 800 milligram tablets should only be used to achieve a daily regimen of 800 milligrams once daily.
This product is available only as film-coated tablets and is therefore not suitable for patients unable to swallow whole tablets, such as young children. For use in these patients, availability of more appropriate formulations containing darunavir should be verified.

Dose for adults who have not previously taken antiretroviral medicines (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, always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. Darunavir Krka d.d. cannot work optimally without cobicistat or ritonavir and without food. You must eat a meal or snack within 30 minutes before taking Darunavir Krka d.d. and cobicistat or ritonavir. The type of food is not important. Even if you feel better, do not stop taking Darunavir Krka d.d. and cobicistat or ritonavir before speaking with your doctor.

Instructions for adults

Take two 400-milligram tablets at the same time, once daily, 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 HIV medicines used in combination with Darunavir Krka d.d. and cobicistat or ritonavir as directed by your doctor

Adults who have previously taken antiretrovirals (your doctor will assess this)
You may require a different dose of Darunavir Krka d.d. that cannot be administered with these 400 or 800 milligram tablets. Other dosage strengths 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 dose is most appropriate.

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

The usual dose of Darunavir Krka d.d. is 800 milligrams once daily (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 older taking ritonavir and aged 12 years and older taking cobicistat, and weighing more than 40 kilograms, who have previously taken antiretroviral medicines (your child’s doctor will determine this condition)
The dose is either:

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 dose is most appropriate.

Instructions for children aged 3 years and older taking ritonavir and aged 12 years and older taking 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 daily, 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 HIV medicines 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
Inform your doctor, pharmacist, or nurse immediately.

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

If you vomit after taking Darunavir Krka d.d. and cobicistat or ritonavir
If you vomit within 4 hours after taking the medicine, you should take another dose of Darunavir Krka d.d. and cobicistat or ritonavir with food as soon as possible. If you vomit more than 4 hours after taking the medicine, you do not need to take another dose of Darunavir Krka d.d. and cobicistat or ritonavir until the next scheduled dose.
Contact your doctor if you are unsure what to do if you miss a dose or vomit.

Do not stop treatment with Darunavir Krka d.d. without first talking to your doctor
Anti-HIV medicines can make you feel better. Do not stop taking Darunavir Krka d.d., even if you feel better. Talk to your doctor first.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Like all medicines, this medicine can cause side effects, although not everyone experiences them.

Inform your doctor if you develop any of the following side effects

Liver problems have been reported, which occasionally may be severe. Your doctor will need to carry out blood tests before starting Darunavir Krka d.d. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or the 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 severity. A rash may also be a symptom of a rare but more serious condition. It is therefore important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether Darunavir Krka d.d. should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (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 bloating, dyspepsia (digestive difficulties), 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, balance difficulties
Breathing difficulties, cough, nosebleeds, throat irritation
Inflammation of the stomach or mouth, heartburn, nausea, dry mouth, abdominal discomfort, constipation, belching
Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
Hives, 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
Slowed thyroid function. This can be detected through blood testing.
High blood pressure, hot flushes
Red or dry eyes
Fever, leg swelling due to fluid accumulation, malaise, chills, unusual sensations, irritability, pain
Symptoms of infection, 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 [a severe rash that may be accompanied by fever, fatigue, facial or lymph node swelling, increased eosinophils (a type of white blood cell), and effects on the liver, kidneys, or lungs]
Heart attack, slow heartbeat, palpitations
Vision disorders
Chills, feeling unwell
A sensation of confusion or disorientation, mood changes, restlessness
Fainting, seizures, changes 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 certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increased levels of certain white blood cells.

Some side effects are typical of anti-HIV medicines belonging to the same class as Darunavir Krka d.d. These include:

Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

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 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 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 carton and on 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 via wastewater 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 substance is darunavir. Each tablet contains 400 mg or 800 mg of darunavir.
The other components are: microcrystalline cellulose, crospovidone, hydroxypropylcellulose, anhydrous colloidal silica, silicified microcrystalline cellulose (microcrystalline cellulose; anhydrous colloidal silica) 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 contents of the pack
Darunavir Krka d.d. 400 mg film-coated tablets (tablets):
Film-coated tablets, yellowish brown, oval, biconvex, engraved with the mark
S1 on one side. Tablet size: 17 x 8.5 mm.
Darunavir Krka d.d. 800 mg film-coated tablets (tablets):
Film-coated tablets, reddish brown, oval, biconvex, engraved with the mark
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 box.
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 box.
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-Straße 5, 27472 Cuxhaven, Germany

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

België/Belgique/Belgien Lietuva
KRKA Belgium, SA. UAB KRKA Lietuva
Tél/Tel: +32 (0) 487 50 73 62 Tel: + 370 5 236 27 40

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

Česká republika Magyarország
KRKA ČR, s.r.o. KRKA Magyarország Kereskedelmi Kft.
Tel: + 420 (0) 221 115 150 Tel.: + 36 (1) 355 8490

Danmark Malta
KRKA Sverige AB E. J. Busuttil Ltd.
Tlf: + 46 (0)8 643 67 66 (SE) Tel: + 356 21 445 885

Deutschland Nederland
TAD Pharma GmbH KRKA Belgium, SA.
Tel: + 49 (0) 4721 606-0 Tel: +32 (0) 487 50 73 62 (BE)

Eesti Norge
KRKA, d.d., Novo mesto Eesti filiaal KRKA Sverige AB
Tel: + 372 (0) 6 671 658 Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα Österreich
KRKA ΕΛΛΑΣ ΕΠΕ KRKA Pharma GmbH, Wien
Τηλ: +30 2100101613 Tel: + 43 (0)1 66 24 300

España Polska
KRKA Farmacéutica, S.L. KRKA-POLSKA Sp. z o.o.
Tel: + 34 911 61 03 80 Tel.: + 48 (0)22 573 7500

France Portugal
KRKA France Eurl KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tél: + 33 (0)1 57 40 82 25 Tel: + 351 (0)21 46 43 650

Hrvatska România
KRKA - FARMA d.o.o. KRKA Romania S.R.L., Bucharest
Tel: + 385 1 6312 100 Tel: + 4 021 310 66 05

Ireland Slovenija
KRKA Pharma Dublin, Ltd. KRKA, d.d., Novo mesto
Tel: + 353 1 413 3710 Tel: + 386 (0) 1 47 51 100

Ísland Slovenská republika
LYFIS ehf. KRKA Slovensko, s.r.o.
Sími: + 354 534 3500 Tel: + 421 (0) 2 571 04 501

Italia Suomi/Finland
KRKA Farmaceutici Milano S.r.l. KRKA Finland Oy
Tel: + 39 02 3300 8841 Puh/Tel: +358 20 754 5330

Κύπρος Sverige
KI.PA. (PHARMACAL) LIMITED Τηλ: + 357 24 KRKA Sverige AB
651 882 Tel: + 46 (0)8 643 67 66 (SE)

Latvija United Kingdom (Northern Ireland)
KRKA Latvija SIA Krka Pharma Dublin, Ltd.
Tel: + 371 6 733 86 10 Tel: +353 1 413 3710

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

Patient information leaflet: information for the patient

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

darunavir
Read this entire leaflet carefully before 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 give it to others, even if their symptoms are the same as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to 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 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. Contents of the pack and other information

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

What is Darunavir Krka d.d.?
Darunavir Krka d.d. contains the active substance darunavir. Darunavir Krka d.d. is an 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 HIV-related diseases.

What is it used for?
Darunavir Krka d.d. is used to treat adults and children aged 3 years and older, weighing at least 15 kilograms, who are infected with HIV and who have previously taken other antiretroviral medicines.
Darunavir Krka d.d. must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. Your doctor will discuss with you the most appropriate combination of medicines for your treatment.

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

Do not take Darunavir Krka d.d.

if you are allergic to the active substance, or to any of the other ingredients of this medicine (listed in section 6),
if you have severe liver problems. Consult your doctor if you are unsure about the severity of your liver disease. Additional tests may be required. Do not take Darunavir Krka d.d. with any of the following medicines If you are currently taking one of these medicines, ask your doctor how to switch to another medicine.

Medicine	Purpose of the medicine
Avanafil	for the treatment of erectile dysfunction
Astemizole or terfenadine	for the treatment of allergic symptoms
Triazolam and oral midazolam (taken by mouth)	used to help sleep and/or reduce anxiety
Cisapride	for the treatment of certain stomach disorders
Colchicine (if you have kidney and/or liver problems)	for the treatment of gout or familial Mediterranean fever
	familial
Lurasidone, pimozide, quetiapine or sertindole	for the treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	for the treatment of migraine
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	for the treatment of certain heart problems, such as abnormal heart rhythms
Lovastatin, simvastatin and lomitapide	to lower cholesterol levels
Rifampicin	for the treatment of certain infections, such as tuberculosis
Lopinavir/ritonavir combination	this anti-HIV medicine belongs to the same class as Darunavir Krka d.d.
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	to treat benign prostatic hyperplasia
Sildenafil	to treat high blood pressure in the pulmonary circulation
Dabigatran, ticagrelor	to help prevent platelet aggregation in the treatment of patients with a history of heart attack
Naloxegol	to treat opioid-induced constipation
Dapoxetine	to treat premature ejaculation
Domperidone	to treat nausea and vomiting

Do not co-administer 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 necessary precautions to avoid transmitting the infection to others.
People taking Darunavir Krka d.d. may still develop infections or other illnesses associated with HIV infection. Regular contact with your doctor is essential.
Patients taking Darunavir Krka d.d. may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin 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 medical condition BEFORE and DURING treatment
Make sure to check the following points and inform your doctor if any of them apply to you.

Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe Darunavir Krka d.d.
Inform your doctor if you have diabetes. Darunavir Krka d.d. may increase blood sugar levels.
Inform your doctor immediately 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 infections, signs and symptoms of inflammation from previous infections may occur soon after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, allowing the body to fight infections that may have been present without causing obvious symptoms.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may occur after starting medications for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in hands and feet spreading toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
Inform your doctor if you have haemophilia. Darunavir Krka d.d. may increase the risk of bleeding.
Inform your doctor if you are allergic to sulphonamides (used to treat certain 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 (death of bone tissue due to reduced blood supply to the bone). Several risk factors for developing this condition include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint swelling, pain, and stiffness (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.
Elderly
Darunavir 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 adolescents
Darunavir Krka d.d. must not be used in children under 3 years of age or weighing less than 15 kg.
Other medicines and Darunavir Krka d.d.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. There are medicines that must not be co-administered with Darunavir Krka d.d. These have been listed previously under the heading “Do not co-administer Darunavir Krka d.d. with any of the following medicines.” In most cases, Darunavir Krka d.d. can be co-administered with anti-HIV medicines belonging 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 must 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 regarding 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 are taking:
Phenobarbital, phenytoin (to prevent epileptic seizures)
Dexamethasone (a corticosteroid)
Efavirenz (to treat HIV infection)
Rifapentine, rifabutin (medicines to treat certain 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 are taking:
Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions),

since 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 estrogens or hormone replacement therapy. Darunavir Krka d.d. may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
Ethinylestradiol/drospirenone. Darunavir Krka d.d. may increase the risk of elevated potassium levels due to drospirenone.
Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
Clarithromycin (antibiotic)
Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity). Since the therapeutic effect or side effects of these medicines may be increased, your doctor may wish to perform additional tests.
Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle disorders, and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under careful monitoring for corticosteroid-related side effects.
Buprenorphine/naloxone (to treat opioid dependence).
Salmeterol (for asthma treatment).
Artemether/lumefantrine (a combination of medicines for treating malaria).
Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)
Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension)
Glecaprevir/pibrentasvir (to treat hepatitis C infection).
Fentanyl, oxycodone, tramadol (for pain treatment).
Fesoterodine, solifenacin (to treat urological disorders).

The dosage of other medicines may need to be adjusted because the therapeutic effect and side effects of these medicines or of Darunavir Krka d.d. may be affected when co-administered.
Inform your doctor if you are taking:

Alfentanil (a potent, short-acting injectable painkiller used during surgery)
Digoxin (to treat certain heart conditions)
Clarithromycin (antibiotic)
Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
Rifabutin (for bacterial infections)
Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation)
Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
Maraviroc (to treat HIV infection)
Methadone (to treat opioid dependence)
Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
Colchicine (to treat gout or familial Mediterranean fever)
Bosentan (to treat high blood pressure in the pulmonary circulation)
Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives)
Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)
This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
Darunavir Krka d.d. with food and drinks
See section 3 “How to take Darunavir Krka d.d.”
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Women who are pregnant or breastfeeding should not take Darunavir Krka d.d. with ritonavir unless specifically instructed by their doctor. Women who are pregnant or breastfeeding should not take darunavir with cobicistat. Women with HIV infection are advised not to breastfeed their infants, both due to the risk of transmitting HIV through breast milk and due to unknown effects of Darunavir Krka d.d. on infants.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking Darunavir Krka d.d.

3. How to take Darunavir Krka d.d.

Take this medicine exactly as stated in this leaflet or as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Even if you feel better, do not stop taking Darunavir Krka d.d. and ritonavir without speaking to your doctor.
After treatment has been started, the dose or dosage form must not be changed, nor must treatment be stopped, without instructions from your doctor.
Darunavir Krka d.d. 600 mg film-coated tablets must not be chewed or crushed.
This dosage strength is not suitable for doses below 600 mg. Not all paediatric doses can be administered with this medicine. Other darunavir tablets with different strengths and formulations are available.

Dose for adults who have not previously taken antiretroviral medicines (your doctor will
assess this)
Different doses 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 medicines (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 daily, 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 daily. The 400 mg and 800 mg tablets of Darunavir Krka d.d. must only be used to construct the 800 mg once-daily regimen. Discuss with your doctor which dose is most appropriate for you.

Instructions for adults

Always take Darunavir Krka d.d. with ritonavir. Darunavir Krka d.d. does not work adequately 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 adequately 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 and older and weighing at least 15 kilograms who have not
previously taken antiretroviral medicines (your child’s doctor will determine this condition)
The doctor will calculate the correct daily dose 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 daily. Your doctor will inform you how many Darunavir Krka d.d. tablets the child should take.

Weight	One dose of Darunavir is	One dose of Ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
more than 40 kilograms	800 milligrams	100 milligrams

Dose for children aged 3 years and older and weighing at least 15 kg (kilograms) who have previously taken antiretroviral medicines (this condition will be determined by the child's doctor)
The doctor will calculate the appropriate dose based on the child's weight (see table below). The doctor will decide whether a once-daily or twice-daily dosing regimen is appropriate for the child. The dose must not exceed the recommended adult dose, which is 600 milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir twice daily, or 800 milligrams of Darunavir Krka d.d. together with 100 milligrams of ritonavir once daily. The doctor will inform you how many Darunavir Krka d.d. tablets and how much ritonavir (capsules, tablets or solution) the child should take. Lower-dose tablets are available, and the doctor may have prescribed a specific combination of tablets to achieve the appropriate dosing regimen.
The doctor will determine whether Darunavir Krka d.d. tablets are suitable for the child.
Twice-daily dosing

Weight	One dose is
between 15 and 30 kilograms	375 milligrams darunavir + 50 milligrams ritonavir twice daily
between 30 and 40 kilograms	450 milligrams darunavir + 60 milligrams ritonavir twice daily
over 40 kilograms*	600 milligrams darunavir + 100 milligrams ritonavir twice daily

*
Once-daily dose

Weight	One dose of Darunavir is	One dose of Ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
more than 40 kilograms	800 milligrams	100 milligrams

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 daily or once daily. If Darunavir Krka d.d. is prescribed twice daily, the child should 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 does not matter.
The child must swallow the tablets with a drink such as water or milk.

If the child takes more Darunavir Krka d.d. than they should
Contact the doctor, pharmacist, or nurse immediately.

If the child forgets to take Darunavir Krka d.d.
If you notice within 6 hours, give the missed dose immediately. Always take the tablets with ritonavir and food. If you notice after 6 hours, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.

In case of vomiting after taking Darunavir Krka d.d. and ritonavir
If vomiting occurs within 4 hours of taking the medicine, give another dose of Darunavir Krka d.d. and ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, do not give another dose of Darunavir Krka d.d. and ritonavir until the next scheduled dose.

Contact the doctor if you have any doubts about what to do if a dose is missed or if vomiting occurs.

Do not stop treatment with Darunavir Krka d.d. without first talking to the doctor
Anti-HIV medicines can make the child feel better. Do not stop taking Darunavir Krka d.d., even if the child feels better. Always talk to the doctor first.
If you have any questions about the use of this medicine, consult the doctor, pharmacist, or nurse.

4. Possible side effects

During HIV therapy, 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, this medicine can cause side effects, although not everybody gets them.

Tell your doctor if you develop any of the following side effects

Liver problems have been reported, which occasionally can be serious. Your doctor will carry out blood tests before starting Darunavir Krka d.d. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or the whites of the eyes, dark-coloured urine (tea-coloured), pale-coloured stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort under the right side of the ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to moderate in severity. A skin rash may also be a symptom of a rare but more serious condition. It is therefore important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether Darunavir Krka d.d. should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (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 bloating, dyspepsia (digestive difficulties), 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
Shortness of breath, 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
Slowed thyroid function. This can be detected by a blood test.
High blood pressure, hot flushes
Red or dry eyes
Fever, leg swelling due to fluid accumulation, malaise, chills, abnormal sensations, irritability, pain
Symptoms of infection, 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 which may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell in the blood), effects on the liver, kidneys or lungs]
Heart attack, slow heartbeat, palpitations
Vision disorders
Chills, feeling of malaise
A feeling of confusion or disorientation, altered mood, restlessness
Fainting, epileptic 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 certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include increased levels of certain white blood cells.

Some side effects are typical of anti-HIV medicines in the same class as Darunavir Krka d.d. These are:

Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects

If you experience any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the reporting system referred to 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 stated on the carton and on 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.
Shelf life after first opening: 3 months.
Do not dispose of any medicine via wastewater 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 substance is darunavir. Each film-coated tablet contains 600 mg of darunavir.
The other components are microcrystalline cellulose, crospovidone, hydroxypropylcellulose, anhydrous colloidal silica, silicified microcrystalline cellulose (microcrystalline cellulose; anhydrous colloidal 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 contents of the pack

Film-coated tablets (tablets) are orange-brown, oval, biconvex, engraved with the code S2 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 with 30 film-coated tablets), 60 film-coated tablets (2 bottles of 30 film-coated tablets each), 90 film-coated tablets (3 bottles of 30 film-coated tablets each), and 180 film-coated tablets (6 bottles of 30 film-coated tablets each) 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-Straße 5, 27472 Cuxhaven, Germany

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

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

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

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

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

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Ελλάδα
KRKA ΕΛΛΑΣ ΕΠΕ
Τηλ: +30 2100101613

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 80

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 413 3710

Ísland
LYFIS ehf.
Sími: + 354 534 3500

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Κύπρος (Cyprus)
KI.PA. (PHARMACAL) LIMITED
Τηλ: + 357 24 651 882

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

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

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

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

Malta
E. J. Busuttil Ltd.
Tel: + 356 21 445 885

Nederland
KRKA Belgium, SA.
Tel: +32 (0) 487 50 73 62 (BE)

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

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Suomi/Finland
KRKA Finland Oy
Puh/Tel: +358 20 754 5330

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

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/