DARUNAVIR KRKA 600 mg FILM-COATED TABLETS

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

Do not take Darunavir Krka

• 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. 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 contact your doctor.

Patient taking Darunavir Krka and raltegravir (for HIV infection), may more frequently 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 disease, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding if 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 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 that starts in the hands and feet and moves up towards the trunk of the body, palpitations, tremor or hyperactivity, inform your doctor immediately to receive necessary treatment.

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

Darunavir Krka is not indicated for children below 3 years of age or weighing less than 15 kg.

Taking Darunavir Krka with other medicines

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 in the section “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 FIs (fusion inhibitors)]. Darunavir Krka has not been tested with all protease inhibitors (PIs) and should 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 tell your doctor and carefully follow their instructions on which medicines can be combined.

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

• Phenobarbital, phenytoin (to prevent seizures)
• Dexamethasone (corticosteroid)
• Efavirenz (for HIV infection)
• Boceprevir (for treating hepatitis C infection)
• Rifapentine, rifabutin (medicines for treating 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 conditions) 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 estrogen and hormone replacement therapy.

Darunavir Krka may reduce their effect. 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). There may be an increased risk of muscle damage. Your doctor will decide which cholesterol-lowering treatment is best 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 conditions, and other inflammatory conditions. 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)
• Salmeterol (medicine for asthma)
• Artemether/lumefantrine (a combination of medicines for treating malaria)
• Dasatinib, everolimus, nilotinib, vinblastine, vincristine (for cancer)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart and lung condition called pulmonary arterial hypertension)
• Simeprevir (for treating hepatitis C infection)
• Fentanyl, oxycodone, tramadol (for pain relief).

In certain cases, it may be necessary to modify the dose of some medicines because when combined, the therapeutic or adverse effects of these or Darunavir Krka may be affected.

Tell your doctor if you are taking:

• Alfentanil (injectable pain reliever with strong and short action used in surgical procedures)
• Digoxin (for certain heart conditions)
• Clarithromycin (antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (for fungal infections). Voriconazole can only be administered after a medical evaluation.
• 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 depression and anxiety)
• Maraviroc (for HIV infection)
• Methadone (for narcotic dependence)
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine (for gout or Mediterranean fever)
• Bosentan (for high blood pressure in the pulmonary circulation)
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, midazolam given by injection, zolpidem (sedatives)
• Perphenazine, risperidone, thioridazine (for psychiatric conditions).

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

Taking Darunavir Krka with food and drinks

See section 3 “How to take Darunavir Krka”.

Pregnancy and breast-feeding

Tell your doctor immediately if you are pregnant, plan to become pregnant, or are breast-feeding. Pregnant or breast-feeding women should not take Darunavir Krka with ritonavir unless specifically advised by their doctor. Pregnant or breast-feeding women should 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 be infected with HIV through breast milk, and also because of the unknown effects of the medicine on the baby.

Driving and using machines

Do not drive or operate machinery if you experience dizziness after taking Darunavir Krka.

3. How to take Darunavir Krka

Follow the administration instructions for the medicine exactly as indicated in the 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 and 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 the doctor.

Darunavir Krka 600 mg film-coated tablets are only available in tablets and are therefore not suitable for patients who cannot swallow tablets whole, such as young children. Darunavir Krka 600 mg film-coated tablets should not be chewed or crushed. For use in these patients, the most suitable formulations containing darunavir should be checked to determine their availability.

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

You will need a different dose of Darunavir Krka that cannot be administered with these 600 mg tablets. Other doses of Darunavir Krka are available.

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

The dose is:

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

Or

• 800 mg of Darunavir Krka (2 tablets containing 400 mg of Darunavir Krka or 1 tablet containing 800 mg of Darunavir Krka) together with 100 mg of ritonavir, once a day. The 400 mg and 800 mg Darunavir Krka tablets should only be used to achieve the daily dose of 800 mg.

Please consult your doctor to determine the correct dose for you.

Instructions foradults

• Take Darunavir Krka always with ritonavir. Darunavir Krka does not work properly without ritonavir.
• In the morning, take 1 tablet of 600 mg of Darunavir Krka together with 100 mg of ritonavir.
• In the evening, take 1 tablet of 600 mg of Darunavir Krka together with 100 mg of ritonavir.
• Take Darunavir Krka with food. Darunavir Krka does not work properly without food. The type of food does not matter.
• Swallow the tablets with a drink, such as water or milk.

Dose for children from 3 years of age, with a weight of at least 15 kg, who have not previously taken antiretroviral medications (to be determined by your doctor in this case)

The doctor will calculate the correct daily dose based on the child's weight (see the table below). This dose should not exceed the recommended adult dose, which is 800 mg of Darunavir Krka together with 100 mg of ritonavir once a day.

The doctor will inform you about how many Darunavir Krka tablets and how much ritonavir (capsules, tablets, or solution) the child should take.

Oral solution of ritonavir: 80 mg per milliliter

Dose for children from 3 years of age, with a weight of at least 15 kg, who have previously taken antiretroviral medications (to be determined by your doctor in this case)

The doctor will establish the correct dose based on the child's weight (see the table below). The doctor will determine if the once-daily or twice-daily dose is suitable for the child. This dose should not exceed the recommended adult dose, which is 600 mg of Darunavir Krka together with 100 mg of ritonavir twice a day or 800 mg of Darunavir Krka together with 100 mg of ritonavir once a day. The doctor will inform you about how many Darunavir Krka tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Lower concentration tablets are available to achieve the appropriate dosing regimen.

Your doctor will determine if Darunavir Krka tablets are suitable for the child.

Dose twice a day

• The doctor will determine if, for children 12 years of age or older and weighing at least 40 kilograms, the Darunavir Krka 800 mg once-daily dose can be used. This dose cannot be administered with the 600 mg tablets. Other formulations of Darunavir Krka are available.

Dose once a day

Oral solution of ritonavir: 80 mg per milliliter

Instructions forchildren

• The child should take Darunavir Krka always with ritonavir. Darunavir Krka cannot work properly without ritonavir.
• The child should take the appropriate dose of Darunavir Krka and ritonavir twice a day or once a day. If Darunavir Krka is prescribed twice a day, the child should take one dose in the morning and one in the evening. The child's doctor will determine the appropriate dosing regimen.
• The child should take Darunavir Krka with food. Darunavir Krka cannot work properly without food. The type of food does not matter.
• The child should swallow the tablets with a drink, such as water or milk.

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 6 hours, take the missed dose immediately. Always with ritonavir and with food. If you realize after 6 hours, skip that dose and continue with the next scheduled dose as usual.

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

If you stop taking Darunavir Krka

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 further 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, which can occasionally be severe. Your doctor will perform a blood test before you start treatment with Darunavir Krka. If you have a chronic hepatitis B or C infection, your doctor will frequently check your blood tests, as there is 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 and the whites of the eyes, darkening (tea-colored) urine, pale stools, nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness in the right side below your 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 develop a rash. Your doctor will advise you on how to manage 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, somnolence, 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 electrocardiogram, rapid heart rate
• decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance
• breathing difficulties, cough, nosebleeds, throat irritation
• stomach or mouth inflammation, heartburn, nausea, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• hives, severe skin and tissue swelling (mainly lips or eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail discoloration
• muscle pain, muscle sensitivity or weakness, muscle cramps, 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, herpes simplex
• erectile dysfunction, breast enlargement
• sleep disorders, somnolence, depression, anxiety, abnormal dreams, decreased libido.

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]
• heart attack, 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 joint pain, 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 of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is possible side effects 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 stated on the carton 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 disposed of via 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 600 mg of darunavir.
• The other ingredients are:
• In the tablet core: microcrystalline cellulose, crospovidone, hydroxypropyl cellulose, colloidal anhydrous silica, microcrystalline cellulose silicate (microcrystalline cellulose; colloidal anhydrous silica), and magnesium stearate (E470b)
• In the tablet coating: polyvinyl alcohol, macrogol, titanium dioxide (E171), talc (E553b), yellow iron oxide (E172), and red iron oxide (E172).

Appearance of Darunavir Krka and package contents

The film-coated tablets are orange-brown, oval, biconvex, and marked with S2 on one side.

Tablet size: 19.5 x 10 mm.

Darunavir Krka is 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 carton.

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 obtain further information on this medication by contacting the local representative of the marketing authorization holder:

This prospectus was last revised

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