DARUNAVIR TARBIS 800 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Darunavir Tarbis 800 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. Storage of Darunavir Tarbis
6. Contents of the pack and further 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 will improve your immune system and reduce the risk of diseases associated with HIV infection.

What is it used for?

The 800-milligram tablet of Darunavir Tarbis is used to treat adults and children (from 3 years of age, weighing at least 40 kilograms) infected with HIV and

• who have not used antiretroviral medicines before.
• in certain patients who have used antiretroviral medicines before (as determined by your doctor).

This medicine must be taken in combination with a low dose of cobicistat or ritonavir and other HIV medicines. Your doctor will explain which combination of medicines is best 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 cobicistat or 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 transmit HIV to others, although effective antiviral treatment reduces this risk. Consult your doctor about the precautions needed to avoid infecting others.

People taking darunavir may develop other infections or diseases associated with HIV. You must remain under regular medical care.

People taking darunavir may develop a skin rash. It is not common for the rash to be severe or life-threatening. Please consult your doctor if you develop a rash.

Patient taking darunavir and raltegravir (for HIV infection) may develop rashes (usually mild or moderate) more frequently than patients taking either of the two medicines separately.

Tell your doctor about your situation BEFORE and DURING your treatment

Make sure you check the following points and inform your doctor if any 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 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, swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation due to previous infections may appear soon after starting HIV treatment. It is believed that these symptoms are due to an improvement in the body's immune response, which enables it to fight off infections that were present without any obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you have started taking medicines for the treatment of your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and rising towards the trunk of the body, palpitations, tremors, or hyperactivity, inform your doctor immediately to 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 using combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by 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 are pain, discomfort, and stiffness of the joints (especially the hip, knee, and shoulder) and difficulty moving. 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 and adolescents

The 800-milligram tablet of Darunavir Tarbis should not be used in children under 3 years of age or weighing less than 40 kilograms.

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 combinedwith 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 FIs (fusion inhibitors)]. Darunavir has not been tested with cobicistat or ritonavir and 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 inform your doctor and follow their instructions carefully on which medicines can be combined.

The following products may reduce the effectiveness of darunavir. Inform 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 effects of other medicines. Inform 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.
• Ethinyl estradiol/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 a higher risk of muscle damage. Your doctor will determine 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 diseases, inflammatory eye, joint, and muscle disorders, and other inflammatory conditions. If alternatives cannot be used, their use should only be done after a 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, 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 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 epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine(for the treatment of gout or familial 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)
• Metformin(for type 2 diabetes treatment).

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

Taking Darunavir Tarbis with food and drinks

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 should not take darunavir with ritonavir unless their doctor specifically instructs them to do so. Pregnant or breastfeeding women should 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 may become infected with HIV through breast milk, as well as the unknown effects of the medicine on the baby.

Driving and using machines

Do not operate tools or machines or drive if you experience dizziness after taking this medicine.

3. How to Take Darunavir Tarbis

Follow the administration instructions for this medication exactly as 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 cobicistat or ritonavir without consulting your doctor first, even if you feel better.

After starting treatment, do not change the dose or form of the dose or interrupt treatment without your doctor's instructions.

Darunavir Tarbis 800 mg tablets are used only for the 800 milligram once-daily regimen.

Dose for Adults Who Have Not Taken Antiretroviral Medications Before (to be determined by your doctor)

The normal dose of Darunavir Tarbis is one 800 mg tablet of Darunavir Tarbis 800 mg film-coated tablets once a day.

You should take darunavir every day and always in combination with 150 mg of cobicistat or 100 mg of ritonavir and with food. Darunavir does not work properly without cobicistat or ritonavir and food. Before taking darunavir and cobicistat or ritonavir, you should eat food 30 minutes beforehand. The type of food is not important. Do not interrupt treatment with darunavir or cobicistat or ritonavir without consulting your doctor first, even if you feel better.

Instructions for Adults

• Take one 800 mg tablet at the same time, once a day, every day.
• Always take darunavir with 150 mg of cobicistat or 100 mg of ritonavir.
• Take the tablets with food.
• Swallow the tablet with a drink, which can be water or milk.
• Take the other HIV medications used in combination with darunavir and cobicistat or ritonavir as your doctor recommends.
• The 100 mg/ml oral suspension of darunavir has been developed for use in children, but in some cases, it may also be used in adults.

Dose for Adults Who Have Taken Antiretroviral Medications Before (to be determined by your doctor)

The dose is:

• 800 mg of darunavir (2 tablets of 400 mg of darunavir or 1 tablet of 800 mg of darunavir) with 150 mg of cobicistat or 100 mg of ritonavir once a day.

or

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

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

Dose for Children from 3 Years of Age, Weighing More Than 40 Kilograms, Who Have Not Taken Antiretroviral Medications Before (to be determined by your child's doctor)

• The usual dose of darunavir is 800 mg (2 tablets of 400 mg of darunavir or 1 tablet of 800 mg of darunavir) with 100 mg of ritonavir once a day.

Dose for Children from 3 Years of Age, Weighing More Than 40 Kilograms, Who Have Taken Antiretroviral Medications Before (to be determined by your child's doctor)

The dose is:

• 800 mg of darunavir (2 tablets of 400 mg of darunavir or 1 tablet of 800 mg of darunavir) with 100 mg of ritonavir once a day.

or

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

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

Instructions for Children from 3 Years of Age, Weighing More Than 40 Kilograms

• Take 800 mg of darunavir (2 tablets of 400 mg of darunavir or 1 tablet of 800 mg of darunavir) at the same time, once a day, every day.
• Always take darunavir with 100 mg of ritonavir.
• Take the tablets with food.
• Swallow the tablets with a liquid, such as water or milk.
• Take the other medications used in combination with darunavir and ritonavir as your doctor recommends.

Child-Resistant Cap Removal

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

• Push the plastic cap down, turning it at the same time 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 12 hours, take the tablets immediately. Always take the dose with cobicistat or ritonavir and with food. If you realize after 12 hours, skip that dose and make the next one as usual. Do not take a double dose to make up for forgotten 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 likelihood 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, 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, alopecia, 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, 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 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 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: 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 they are possible side effects not listed in this prospectus.

You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: 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 thrown down the drain or into the trash. Deposit the packaging and medications you no longer need at the SIGRE 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 800 mg Film-Coated Tablets

The active ingredient is darunavir. Each tablet contains 800 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 800 mg Film-Coated Tablets and Package Contents

Oval, biconvex, film-coated yellow tablets, approximately 20.2 mm in length and 10.1 mm in width, engraved with a 'V' on one side and a '7' 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 polypropylene (HDPE) white opaque 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 30 or 90 (3 bottles of 30) film-coated tablets.

Not all pack sizes may be marketed.

Darunavir Tarbis is also available in 400 mg and 600 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 800 mg filmomhulde tabletten

Sweden: Darunavir Amarox 800 mg Filmdragerade tabletter

Germany: Darunavir Amarox 800 mg Filmtabletten

Spain: Darunavir Tarbis 800 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/)