DARUNAVIR KRKA 400 mg FILM-COATED TABLETS

2. What you need to know before you take Darunavir Krka

Do not take DarunavirKrka

• if you are allergic to the active substance or any of the other ingredients of this medicine (listed in section 6).
• if you have severe liver problems. Ask your doctor if you are not sure about the severity of your liver disease. You may need to have some additional tests.

Do not take Darunavir Krka with any of the following medicines:

If you are taking any of these medicines, consult your doctor to change to another medicine.

Do not take Darunavir Krka with products containing St. John's Wort (Hypericum perforatum).

Warnings and precautions

Consult your doctor, pharmacist or nurse before you start taking Darunavir Krka.

Darunavir Krka does not cure HIV infection. While you are taking this medicine, you may still develop infections or other illnesses associated with HIV infection. Keep in regular contact with your doctor.

People taking Darunavir Krka may develop skin rash. It is not common for the rash to be severe or potentially life-threatening. However, if you develop a rash, please consult your doctor.

Patients taking Darunavir Krka and raltegravir (for HIV infection) may be more likely to develop rash (usually mild or moderate) than patients taking either of these medicines separately.

Tell your doctor about your situation BEFORE and DURING treatment

Make sure you check the following points and tell your doctor if any of them apply to you.

• Tell your doctor if you have had any liver problems, including infection with hepatitis B or C. Your doctor will assess the severity of your liver disease before deciding whether you can take Darunavir Krka.
• Tell your doctor if you have diabetes. Darunavir Krka may increase blood sugar levels.
• Tell your doctor immediately if you notice any symptoms of infection (such as enlarged 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 anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body's immune response, enabling it to fight off infections that have been present without causing symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition where the immune system attacks healthy body tissue) may also occur after you have started taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, tell your doctor immediately for the necessary treatment.
• Tell your doctor if you have hemophilia. Darunavir Krka may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients using combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to lack of blood supply to the bone). Many factors can increase the risk of developing this disease, including long-term use of combination antiretroviral therapy, use of corticosteroids, alcohol consumption, severe immune suppression, and higher body mass index. Signs of osteonecrosis include pain, tenderness, and stiffness in the joints (especially the hip, knee, and shoulder) and difficulty walking. If you notice any of these symptoms, please consult your doctor.

Elderly population

Darunavir Krka has only been used in a limited number of patients aged 65 years or older. If you belong to this age group, please consult your doctor to see if you can use Darunavir Krka.

Children andadolescents

Darunavir Krka 400 mg and 800 mg tablets must not be used in children under 3 years of age or weighing less than 40 kg.

Taking Darunavir Krka with othermedicines

Tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines.

Some medicines must not be takenwith Darunavir Krka. The list can be found under the heading “Do not take Darunavir Krka with any of the following medicines:”

In most cases, Darunavir Krka can be taken with HIV medicines from other classes [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and fusion inhibitors]. Darunavir Krka has not been tested with cobicistat or ritonavir and all protease inhibitors (PIs) and must not be used with other HIV protease inhibitors. In some cases, it may be necessary to change the dose of the other medicines. Therefore, if you are taking other anti-HIV medicines, always consult your doctor and follow their instructions carefully on which medicines can be combined.

The following products may reduce the effectiveness of Darunavir Krka. Tell your doctor if you are taking:

• Phenobarbital, phenytoin (to prevent seizures)
• Dexamethasone (corticosteroid)
• Efavirenz (for HIV infection)
• Boceprevir (to treat hepatitis C infection)
• Rifapentine, rifabutin (medicines to treat certain infections such as tuberculosis)
• Saquinavir (for HIV infection).

Darunavir Krka may also affect the action of other medicines. Tell your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disorders) because the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, dabigatran etexilate, rivaroxaban, warfarin (to reduce blood clotting) because the therapeutic or adverse effects of these medicines may be altered; your doctor may perform blood tests.
• Hormonal contraceptives based on estrogens and hormone replacement therapy. Darunavir Krka may reduce their effectiveness. For birth control, alternative non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. Darunavir Krka may increase the risk of elevated potassium levels due to the effect of drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower blood cholesterol levels). There may be an increased risk of muscle damage. Your doctor will determine which cholesterol-lowering treatment is most suitable for you based on your personal circumstances.
• Clarithromycin (antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system) because the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel disease, inflammatory eye, joint, and muscle diseases, and other inflammatory diseases. If alternatives cannot be used, their use should only be done after clinical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.
• Buprenorphine/naloxone (medicines for opioid dependence treatment)
• Salmeterol (medicine for asthma treatment)
• Artemether/lumefantrine (a combination of medicines to treat malaria)
• Dasatinib, everolimus, nilotinib, vinblastine, vincristine (for cancer treatment)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension)
• Simeprevir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (for pain treatment).

This is nota complete list of medicines. Tell your doctor about allthe medicines you are taking.

Taking Darunavir Krka with food anddrinks

See section 3 “How to take Darunavir Krka.”

Pregnancy andbreast-feeding

Tell your doctor immediately if you are pregnant, plan to become pregnant, or are breast-feeding. Pregnant or breast-feeding women must not take Darunavir Krka with ritonavir unless their doctor has specifically told them to do so. Pregnant or breast-feeding women must not take Darunavir Krka with cobicistat.

It is recommended that women infected with HIV do not breast-feed their babies because there is a possibility that the babies could become infected with HIV through their breast milk, and because of the unknown effects of the medicine on the babies.

Driving and usingmachines

Do not drive or use machines if you feel dizzy after taking Darunavir Krka.

3. How to take Darunavir Krka

Follow the administration instructions for the medicine indicated by this prospectus or by your doctor, pharmacist, or nurse. In case of doubt, ask your doctor, pharmacist, or nurse.

Even if you feel better, do not stop taking Darunavir Krka or ritonavir without consulting your doctor.

Once treatment has started, the dose or form of the dose should not be changed, nor should treatment be interrupted without consulting a doctor.

Darunavir Krka 400 mg and 800 mg tablets should only be used to achieve a daily dose of 800 mg.

This product is only available as film-coated tablets and is therefore not suitable for patients who cannot swallow tablets whole, such as young children. For use in these patients, the most suitable formulations containing darunavir should be checked to determine their availability.

Dose for adults who have not taken antiretroviral medications before (to be determined by your doctor)

The usual dose of Darunavir Krka is 800 mg daily (2 tablets containing 400 mg of Darunavir Krka each or 1 tablet containing 800 mg of Darunavir Krka).

You must take Darunavir Krka every day and always in combination with 100 mg of ritonavir and with food. Darunavir Krka does not work properly without ritonavir or without food. You must eat or have a snack 30 minutes before taking Darunavir Krka and ritonavir. The type of food does not matter. Even if you feel better, do not suspend treatment with Darunavir Krka and ritonavir without consulting your doctor.

Instructions for adults

• Take 2 tablets of 400 mg at the same time or 1 tablet of 800 mg, once a day, every day.
• Always take Darunavir Krka with 100 mg of ritonavir.
• Take Darunavir Krka with food.
• Swallow the tablets with a drink like water or milk.
• Take your other HIV medications in combination with Darunavir Krka and ritonavir, as your doctor recommends.

Dose for adults who have taken antiretroviral medications before (to be determined by your doctor)

You may require a different dose of Darunavir Krka that cannot be administered with 400 mg or 800 mg tablets. There are other formulations of Darunavir Krka available.

The dose is:

• 800 mg of Darunavir Krka (2 tablets containing 400 mg of Darunavir Krka each or 1 tablet containing 800 mg of Darunavir Krka) with 100 mg of ritonavir, once a day.

Or

• 600 mg of Darunavir Krka (1 tablet containing 600 mg of Darunavir Krka) with 100 mg of ritonavir, twice a day.

Please talk to your doctor to find out what dose is correct for you.

Dose for children from 3 years of age, with at least 40 kg of weight, who have not taken antiretroviral medications before (to be determined by your doctor in this case)

• The usual dose of Darunavir Krka is 800 mg (2 tablets containing 400 mg of Darunavir Krka each or 1 tablet containing 800 mg of Darunavir Krka) with 100 mg of ritonavir, once a day.

Dose for children from 3 years of age, with at least 40 kg of weight, who have taken antiretroviral medications before (to be determined by your doctor in this case)

The dose is:

• 800 mg of Darunavir Krka (2 tablets containing 400 mg of Darunavir Krka each or 1 tablet containing 800 mg of Darunavir Krka) with 100 mg of ritonavir, once a day.

Or

• 600 mg of Darunavir Krka (1 tablet containing 600 mg of Darunavir Krka) with 100 mg of ritonavir, twice a day.

Please talk to your doctor to find out what dose is correct for you.

Instructions for children from 3 years of age, with at least 40 kg of weight

• Take 800 mg of Darunavir Krka (2 tablets containing 400 mg of Darunavir Krka each or 1 tablet containing 800 mg of Darunavir Krka) at the same time, once a day, every day.
• Always take Darunavir Krka with 100 mg of ritonavir.
• Take Darunavir Krka with food.
• Swallow the tablets with a drink like water or milk.
• Take your other HIV medications in combination with Darunavir Krka and ritonavir or another pharmacokinetic enhancer, as your doctor recommends.

If you take more Darunavir Krka than you should

Inform your doctor or pharmacist immediately.

If you forget to take Darunavir Krka

If you realize within 12 hours, take the missed dose immediately. Always with ritonavir and with food. If you realize after 12 hours, skip that dose and make the next dose as usual.

Do not take a double dose to make up for missed doses.

Do not stop taking Darunavir Krka without talking to your doctor first

HIV medications can make you feel better. Even if you feel better, do not stop taking Darunavir Krka. Consult your doctor first.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

Like all medications, this medication can cause side effects, although not everyone will experience them.

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

There have been reports of liver problems that can occasionally be severe. Your doctor will perform a blood test before you start treatment with Darunavir Krka. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood tests, as there is a higher likelihood of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These can include yellowing of the skin and the whites of the eyes, darkening (tea color) of the urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness in the right side below the ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. The skin rash is usually mild to moderate. A skin rash can also be a symptom of a rare and serious situation. Therefore, it is essential to talk to your doctor if you have a rash. Your doctor will advise you on how to control the symptoms or if you should stop taking Darunavir Krka.

Other serious side effects were diabetes (frequent) and pancreatitis (uncommon).

Very common side effects (may affect more than 1 in 10 patients)

• diarrhea.

Common side effects (may affect up to 1 in 10 patients)

• vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence
• headache, fatigue, dizziness, drowsiness, numbness, tingling, or pain in the hands or feet, weakness, difficulty staying asleep

Uncommon side effects (may affect up to 1 in 100 patients)

• chest pain, changes in the electrocardiogram, rapid heart rate
• decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance
• breathing difficulties, cough, nasal bleeding, throat irritation
• stomach or mouth inflammation, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• hives, severe swelling of the skin and other tissues (especially the lips or eyes),

eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail discoloration

• muscle pain, muscle sensitivity or weakness, muscle cramps, or weakness, pain in the limbs, osteoporosis
• reduced thyroid gland function. This can be seen in a blood test.
• increased blood pressure, flushing
• red or dry eyes
• fever, swelling of the lower limbs due to fluid retention, discomfort, irritability, pain
• infection symptoms, simple herpes
• erectile dysfunction, breast enlargement
• sleep disorders, drowsiness, depression, anxiety, abnormal dreams, decreased sexual desire.

Rare side effects (may affect up to 1 in 1,000 patients)

• a reaction called DRESS [severe rash, which can be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage]
• myocardial infarction, slow heart rate, palpitations
• visual impairment
• chills, strange sensation
• a feeling of confusion or disorientation, altered mood, agitation
• fainting, epileptic seizure, changes or loss of taste
• mouth ulcers, vomiting blood, lip inflammation, dry lips, tongue with thrush
• nasal discharge
• skin lesions, dry skin
• muscle stiffness or in the joints, joint pain with or without inflammation
• changes in some blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: an increase in some white blood cells.

Some side effects are typical of HIV medications that belong to the same family as Darunavir Krka. These are:

• muscle pain, sensitivity, or weakness. In rare cases, these muscle disorders can be severe.

Reporting side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Darunavir Krka

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the box and bottle, after EXP. The expiration date refers to the last day of the month indicated.

Keep the bottle tightly closed to protect it from moisture.

Validity period after first opening: 3 months

Medications should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any medication you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Darunavir Krka

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

Appearance of Darunavir Krka and package contents

The 400 mg Darunavir Krka tablets are:

Yellowish-brown, oval, biconvex film-coated tablets (tablets), marked with S1 on one side.

Tablet size: 17 x 8.5 mm.

The 800 mg Darunavir Krka tablets are:

Reddish-brown, oval, biconvex film-coated tablets (tablets), marked with S3 on one side.

Tablet size: 20 x 10 mm.

Darunavir Krka 400 mg film-coated tablets are available in bottles containing 30 tablets (1 bottle with 30 tablets), 60 tablets (2 bottles, each with 30 tablets), 90 tablets (3 bottles, each with 30 tablets), and 180 tablets (6 bottles, each with 30 tablets) in a box.

Darunavir Krka 800 mg film-coated tablets are available in bottles containing 30 tablets (1 bottle with 30 tablets), 60 tablets (2 bottles, each with 30 tablets), and 90 tablets (3 bottles, each with 30 tablets) in a box.

Not all pack sizes may be marketed.

Marketing authorization 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

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

This prospectus was last revised

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