DARUNAVIR TARBIS 600 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Darunavir Tarbis 600 mg film-coated tablets EFG

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Darunavir Tarbis and what is it used for

What is Darunavir Tarbis?

Darunavir Tarbis contains the active substance darunavir. Darunavir Tarbis is an antiretroviral medicine used in the treatment of infection by the Human Immunodeficiency Virus (HIV). It belongs to a group of medicines called protease inhibitors. Darunavir Tarbis reduces the amount of HIV in your body. This improves your immune system and reduces the risk of diseases associated with HIV infection.

What is it used for?

Darunavir Tarbis is used to treat adults and children from 3 years of age and at least 15 kg in weight, who are infected with HIV and have already used other antiretroviral medicines.

Darunavir Tarbis must be taken with a low dose of ritonavir and other HIV medicines. Your doctor will discuss with you the most suitable combination of medicines for you.

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

Do not take Darunavir Tarbis

• if you are allergicto darunavir or any of the other ingredients of this medicine (listed in section 6) or to ritonavir.
• 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 combine Darunavir Tarbis with any of the following medicines

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

Do not combine this medicine with products containing St. John's Wort (Hypericum perforatum).

Warnings and precautions

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

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

Patients taking darunavir and raltegravir (for HIV infection) may develop rash (usually mild or moderate) more often than patients taking either of these medicines separately.

Tell your doctor about your situation BEFORE and DURING your 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 liver disease, including infection with hepatitis B or C. Your doctor will assess the severity of your liver disease before deciding if you can take this medicine.
• Tell your doctor if you have diabetes. Darunavir may increase blood sugar levels.
• Tell your doctor immediately if you notice any symptoms of infection(for example, enlarged lymph nodes, 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 were already present but not yet 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 starting in the hands and feet and moving up towards the trunk of the body, palpitations, tremor, or hyperactivity, tell your doctor immediately so that you can receive the necessary treatment.
• Tell your doctor if you have hemophilia. Darunavir may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides(for example, used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients taking combination antiretroviral therapy may develop a condition called osteonecrosis (death of bone tissue due to loss of blood supply to the bone). The risk of osteonecrosis is increased in patients with advanced HIV disease or long-term use of combination antiretroviral therapy, or with other risk factors such as use of corticosteroids, excessive alcohol consumption, severe immunosuppression, or higher body mass index. Signs of osteonecrosis include pain, tenderness, and stiffness of 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 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 this medicine.

Children

Darunavir Tarbis is not used in children under 3 years of age or weighing less than 15 kg.

Taking Darunavir Tarbis 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 this medicine. The list can be found in the section “Do not combine Darunavir Tarbis with any of the following medicines:”

In most cases, darunavir can be combined 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 has not been tested with ritonavir with all protease inhibitors 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 effect of darunavir. 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 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, edoxaban, 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 may reduce their effectiveness. For birth control, alternative non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. Darunavir 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 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 a clinical assessment and under close monitoring by your doctor to evaluate 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, irinotecan, nilotinib, vinblastine, vincristine(for cancer treatment)
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir, simeprevir(to treat hepatitis C infection)
• Fentanyl, oxycodone, tramadol(for pain treatment)
• Fesoterodine, solifenacin(for urological disorders treatment).

In certain cases, it may be necessary to modify the dose of some medicines since their combination may affect the therapeutic or adverse effects of these or of darunavir.

Tell your doctor if you are taking:

• Alfentanil(a strong and short-acting injectable pain reliever used in surgical procedures)
• Digoxin(for the treatment of certain heart disorders)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat 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 treatment)
• Maraviroc(for HIV infection treatment)
• Methadone(for narcotic dependence treatment)
• Carbamazepine, clonazepam(to prevent seizures or to treat certain types of neuropathic pain)
• Colchicine(for the treatment of gout or Mediterranean fever)
• Bosentan(for the treatment of high blood pressure in the pulmonary circulation)
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(for psychiatric conditions treatment).

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

Taking Darunavir Tarbis with food and drink

See section 3 “How to take Darunavir Tarbis”

Pregnancy and breastfeeding

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

It is recommended that women infected with HIV do not breastfeed their babies because there is a possibility that the babies could be infected with HIV through breast milk, as well as the unknown effects of the medicine on the baby.

Driving and using machines

Do not drive or use machines if you feel dizzy after taking this medicine.

3. How to take Darunavir Tarbis

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

Do not stop taking darunavir or ritonavir without consulting your doctor first, even if you feel better.

Once treatment has started, the dose or form of the dose should not be changed or treatment interrupted without consulting the doctor.

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

You will require a different dose of darunavir that cannot be administered with these 600-milligram tablets. Other concentrations of Darunavir Tarbis are available.

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

The dose is:

• 600 milligrams of darunavir (1 tablet of 600 milligrams of darunavir) along with 100 milligrams of ritonavir twice a day.

You

• 800 milligrams of darunavir (2 tablets of 400 milligrams of darunavir or 1 tablet of 800 milligrams of darunavir) along with 100 milligrams of ritonavir once a day. The 400-milligram and 800-milligram tablets of darunavir are used only to obtain the 800-milligram once-daily dose.

Please talk to your doctor about which dose is correct for you.

Instructions for adults

• Take darunavir always along with ritonavir. Darunavir does not work properly without ritonavir.
• In the morning, take one 600-milligram tablet of darunavir along with 100 milligrams of ritonavir.
• In the evening, take one 600-milligram tablet of darunavir along with 100 milligrams of ritonavir.
• Take the tablets with food. Darunavir does not work properly without food. The type of food is not important.
• Swallow the tablets with a drink, which can be water or milk.
• Darunavir tablets are available in lower strengths and as an oral suspension for patients with swallowing problems.

Dose for children from 3 years of age, with at least 15 kilograms of weight, who have not taken antiretroviral medications before (to be determined by your child's doctor)

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 milligrams of darunavir along with 100 milligrams of ritonavir once a day.

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

Oral solution of ritonavir: 80 milligrams per milliliter

Dose for children from 3 years of age, with at least 15 kilograms of weight, who have taken antiretroviral medications before (to be determined by your child's doctor)

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 milligrams of darunavir along with 100 milligrams of ritonavir twice a day or 800 milligrams of darunavir along with 100 milligrams of ritonavir once a day. The doctor will inform you about how many darunavir tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Lower-strength tablets are available to achieve the appropriate dose. Darunavir oral suspension is also available.

Dose twice a day

• The child's doctor will determine if the 800-milligram once-daily dose can be used for children 12 years of age or older and weighing at least 40 kilograms. This dose cannot be administered with the 600-milligram tablets. Other presentations of darunavir are available.

Dose once a day

Oral solution of ritonavir: 80 milligrams per milliliter

Instructions for children

• The child should take darunavir always along with ritonavir. Darunavir does not work properly without ritonavir.
• The child should take the correct dose of darunavir and ritonavir twice a day or once a day. If darunavir is prescribed twice a day, the child should take one dose in the morning and another in the evening. The child's doctor will determine the appropriate dosing schedule for the child.
• The child should take darunavir with food. Darunavir does not work properly without food. The type of food is not important.
• The child should swallow the tablets with a drink, such as water or milk.
• Darunavir is available in lower strengths and as an oral suspension for patients with swallowing problems.

Child-resistant cap removal

The plastic bottle has a child-resistant closure and is opened as follows:

• Push the plastic cap down while turning it counterclockwise.
• Remove the cap by unscrewing.

If you take more Darunavir Tarbis than you should

Inform your doctor, pharmacist, or nurse immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Darunavir Tarbis

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

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

HIV medications can make you feel better. Even if you feel better, do not stop taking this medication. 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 treatment, there may be an increase in weight and glucose and lipid levels in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication can cause side effects, although not all people 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 starting treatment with darunavir. 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 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 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 develop a rash. Your doctor will advise you on how to control the symptoms or if you should stop taking darunavir.

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, upper abdominal pain (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 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, nausea, 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 (mainly 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.
• hypertension (high 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, somnolence, 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 may 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 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: increased white blood cells.

Some side effects are typical of HIV medications that belong to the same family as darunavir. 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, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Darunavir Tarbis

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.

This medication does not require special storage conditions.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and unused medications at the SIGRE collection point in the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Darunavir Tarbis 600 mg film-coated tablets EFG

• The active ingredient is darunavir. Each tablet contains 600 mg of darunavir.
• The other ingredients are anhydrous colloidal silica (E551), silicified microcrystalline cellulose (E460), crospovidone (E1202), and magnesium stearate (E470b). The tablet coating contains partially hydrolyzed polyvinyl alcohol, macrogol, titanium dioxide (E171), talc (E553b), and yellow iron oxide (E172).

Appearance of Darunavir Tarbis 600 mg film-coated tablets EFG and package contents

Oval, biconvex, film-coated tablets, yellow in color, approximately 17.9 mm in length and 9.0 mm in width, engraved with a 'V' on one side and a '5' on the other.

Blister pack:

Aluminum blisters in a cardboard box. Each box contains single-dose film-coated tablets in blisters of 30 x 1, 60 x 1, or 90 x 1 units.

Plastic bottle:

High-density polyethylene (HDPE) white opaque plastic bottle in a cardboard box. The bottle contains a desiccant gel silica container. This container should be left inside the bottle to protect the tablets and should not be swallowed.

Each box contains 60 film-coated tablets.

Darunavir Tarbis is also available in 400 mg and 800 mg film-coated tablets.

Marketing authorization holder and manufacturer

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

PLA 3000 Paola

Malta

Amarox Pharma B.V.

Rouboslaan 32

2252 TR Voorschoten

Netherlands

This medication is authorized in EEA Member States under the following names:

Netherlands: Darunavir Amarox 600 mg filmomhulde tabletten

Sweden: Darunavir Amarox 600 mg Filmdragerade tabletter

Germany: Darunavir Amarox 600 mg Filmtabletten

Spain: Darunavir Tarbis 600 mg comprimidos recubiertos con película EFG

Date of the last revision of this prospectus:March 2020

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)