Package Leaflet: Information for the User

Darunavir Tarbis 800 mg Film-Coated Tablets

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

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

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

2. What you need to know before you start taking Darunavir Tarbis

3. How to take Darunavir Tarbis

4. Possible side effects

5. Storage of Darunavir Tarbis

6. Contents of the pack and additional information

What is Darunavir Tarbis?

Darunavir Tarbis contains the active ingredient darunavir. Darunavir Tarbis is an antiretroviral medication used in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medications called protease inhibitors. Darunavir Tarbis reduces the amount of HIV present in the body. This will improve the immune system and decrease the risk of developing diseases associated with HIV infection.

What is it used for?

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

• who have not used antiretroviral medications before.
• in certain patients who have used antiretroviral medications before (this will be determined by your doctor).

This medication must be taken with a low dose of cobicistat or ritonavir and other HIV medications. Your doctor will explain the most suitable combination of medications for you.

Do not take Darunavir Tarbis

• if you areallergicto darunavir or to any of the other components of this medication (listed in section 6) or to cobicistat or to ritonavir.
• if you havesevere liver problems. Ask your doctor if you are unsure of the severity of your liver disease. You may need to have some additional tests.

Do not combine Darunavir Tarbis with any of the following medications

If you are taking any of these medications, consult your doctor to change to another medication.

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Darunavir Tarbis.

Darunavir does not cure HIV infection. While taking this medication, you may still transmit HIV to others, although effective antiviral treatment reduces the risk. Consult your doctor about what precautions are necessary to avoid infecting others.

People taking darunavir may develop other infections or diseases associated with HIV infection. You should maintain regular contact with your doctor.

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

Patients taking darunavir and raltegravir (for HIV infection) may experience rashes (usually mild or moderate) more frequently than patients taking either medication separately.

Inform your doctor about your situation 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 had anyliver disease, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding if you can take this medication.
• Inform your doctor if you havediabetes. Darunavir may cause an increase in blood sugar levels.
• Inform your doctor immediately if you notice anysymptoms of infection(such as 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 shortly after starting HIV treatment. It is believed that these symptoms are due to an improvement in the body's immune response, which allows the body to fight off infections that were present without apparent symptoms.
• Additionally, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may develop after you start taking medications for HIV treatment. These autoimmune disorders may appear many months after treatment initiation. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and ascending to the trunk of the body, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you havehemophilia. Darunavir may increase the risk of bleeding.
• Inform your doctor if you areallergic to sulfonamides(such as those used to treat certain infections).
• Inform your doctor if you notice anybone or muscle problems. Some patients using combination antiretroviral therapy may develop a condition called osteonecrosis (bone death caused by a lack of blood supply to the bone). Several factors increase the risk of developing this disease, including the duration of combination antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, and a higher body mass index. Signs of osteonecrosis include pain, discomfort, and stiffness of the joints (especially the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please consult your doctor.

Geriatric 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 speak with your doctor to see if you can use this medication.

Children and adolescents

The Darunavir Tarbis 800 mg film-coated tablet is not intended for use in children under 3 years of age or weighing less than 40 kg.

Taking Darunavir Tarbis with other medications

Inform your doctor or pharmacist if you are taking or have recently taken any other medication.

Some medicationsshould not be combinedwith this medication. The list can be consulted in the section “Do not combine Darunavir Tarbis with any of the following medications:”

In most cases, darunavir can be combined with HIV medications belonging to other classes [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and IFs (fusion inhibitors)]. Darunavir has not been tested with cobicistat or ritonavir with all protease inhibitors (PIs) and should not be used with other HIV protease inhibitors. In some cases, the dose of the other medications may need to be adjusted. Therefore, if you are taking other HIV medications, inform your doctor and carefully follow their instructions on which medications can be combined.

The following products may reduce the effectiveness of darunavir. Inform your doctor if you take:

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

Darunavir may also affect the effects of other medications. Inform your doctor if you take:

• 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 medications may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin(to reduce blood coagulation) because the therapeutic or adverse effects of these medications may be altered; your doctor may perform blood tests.
• Oral contraceptives based on estrogens and hormone replacement therapy. Darunavir may reduce their effectiveness. For birth control, alternative non-hormonal methods are recommended.
• Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels due to the drospirenone effect.
• Atorvastatin, pravastatin, rosuvastatin(to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine which cholesterol-lowering treatment is best for you based on your individual circumstances.
• Clarithromycin(antibiotic)
• Ciclosporin, everolimus, tacrolimus, sirolimus(to inhibit the immune system) because the therapeutic or adverse effects of these medications may be increased. Your doctor may perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.These medications are used to treat allergies, asthma, inflammatory bowel disease, eye, joint, and muscle inflammation, and other inflammatory conditions. If alternatives cannot be used, their use should only be made after a clinical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.
• Buprenorphine/naloxone(medications for opioid dependence treatment)
• Salmeterol(asthma medication)
• Artemether/lumefantrine(a combination of medications to treat malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine(to treat cancer)
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or to treat a heart and lung disorder called pulmonary hypertension)
• Glecaprevir/pibrentasvir, simeprevir(to treat hepatitis C infection)
• Fentanyl, oxycodone, tramadol(for pain relief)
• Fesoterodine, solifenacin(for urological disorders).

In certain cases, the dose of some medications may need to be adjusted as they may be affected by darunavir or vice versa.

Inform your doctor if you take:

• Alfentanil(injection analgesic with strong and short action used in surgical procedures)
• Digoxin(for heart disorders)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole should only be administered after a medical evaluation.
• 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(for depression and anxiety)
• Maraviroc(for HIV infection)
• Methadone(for opioid dependence treatment)
• Carbamazepine, clonazepam(to prevent seizures or treat certain types of neuropathic pain)
• Colchicine(for gout or Mediterranean fever)
• Bosentan(for pulmonary hypertension)
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(for psychiatric conditions)
• Metformin(for type 2 diabetes).

Thisis not a complete list of medications. Inform your doctor aboutallthe medications you are taking.

Taking Darunavir Tarbis with food and drinks

See section 3 “How to take Darunavir Tarbis”

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 with ritonavir unless their doctor specifically instructs them to do so.Pregnant women or breastfeeding mothers should not take darunavir with cobicistat.

It is recommended that HIV-infected women do not breastfeed their children, as there is a possibility that the children may become infected with HIV through breast milk, as well as unknown effects of the medication on children.

Driving and operating machinery

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

Follow exactly the administration instructions of this medication contained in this leaflet or those 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, even if you feel better.

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

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

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

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

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

Instructions for adults

• Take one 800 milligram tablet at the same time, once a day, every day.
• Take darunavir always with 150 milligrams of cobicistat or 100 milligrams 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 oral suspension of darunavir 100 milligrams per milliliter has been developed for use in children, but in some cases it may also be used in adults.

Dosage for adults who have taken antiretroviral medications before (will be determined by your doctor)

The dose is:

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

or

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

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

Dosage for children 3 years of age or older, weighing more than 40 kilograms who have not taken antiretroviral medications before (will be determined by your child's doctor)

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

Dosage for children 3 years of age or older, weighing more than 40 kilograms who have taken antiretroviral medications before (will be determined by your child's doctor)

The dose is:

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

or

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

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

Instructions for children 3 years of age or older, weighing more than 40 kilograms

• Take 800 milligrams of darunavir (2 tablets of 400 milligrams of darunavir or 1 tablet of 800 milligrams of darunavir) at the same time, once a day, every day.
• Take darunavir always with 100 milligrams 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.

Removing the child-resistant cap

The plastic bottle has a child-resistant cap and opens as follows:

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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Darunavir Tarbis

If you realize within12 hours, take the tablets immediately. Always take the dose with cobicistat or ritonavir and with food. If you realizeafter 12 hours, omit that dose and make the next one in the usual way. Do not take a double dose to compensate for the missed doses.

Do not stop taking Darunavir Tarbis without talking to your doctor

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.

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

Like all medications, this medication can produce side effects, although not all people will experience them.

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

There have been reports of liver problems that may 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 test results, as there is a higher probability 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 white of the eyes, darkening (tea color) of the urine, pale stools (intestinal movements), nausea, vomiting, loss of appetite, or pain, feeling of pain or discomfort 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 severe condition. 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 discontinue darunavir.

Other severe side effects were diabetes (frequent) and pancreatitis (infrequent).Frequent 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, drowsiness, numbness, tingling, or pain in the hands or feet, loss of strength, difficulty falling asleep.

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

• chest pain, changes in the electrocardiogram, rapid heart movements
• decreased or abnormal sensitivity in the skin, numbness, attention disorder, memory loss, difficulty maintaining balance
• difficulty breathing, cough, nasal bleeding, throat irritation
• inflammation of the stomach or mouth, heartburn, nausea, dry mouth, abdominal discomfort, constipation, belching
• renal insufficiency, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• urticaria, severe skin swelling and other tissues (especially the lips or eyes), eczema, excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration
• muscle pain, muscle cramps, or weakness, joint pain, osteoporosis
• reduced thyroid function. This can be seen in a blood test.
• hypertension (increased blood pressure), flushing
• red or dry eyes
• fever, swelling of the lower extremities due to fluid retention, discomfort, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction, breast enlargement
• difficulty falling asleep, drowsiness, 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, facial swelling or lymph node enlargement, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage]
• myocardial infarction, slow heart movements, palpitations
• visual disturbances
• chills, strange sensation
• a feeling of confusion or disorientation, altered mood, agitation
• syncope, seizure, changes or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, tongue with plaque
• nasal secretion
• skin lesions, dry skin
• muscle stiffness or joint stiffness, joint pain with or without inflammation
• changes in some blood cell or biochemistry values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: increased levels of some 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 type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus.

You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and the bottle, after CAD. 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 drains or trash. Dispose of the containers and medications you no longer need at the SIGRE collection point at the pharmacy.Ask your pharmacist how to dispose of the containers and medications you no longer need if you are unsure. By doing so, you will help protect the environment.

Darunavir Tarbis 800 mg Film-Coated Tablets Composition

The active ingredient is darunavir. Each tablet contains 800 mg of darunavir. The other components are anhydrous colloidal silica (E551), 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 Packaging Contents

Oval, biconvex film-coated tablets, approximately 20.2 mm in length and 10.1 mm in width, with a 'V' on one face and a '7' on the other, in a yellow film coating.

Blister Packaging:

Aluminum blisters in a cardboard box. Each box contains unit doses of 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 plastic bottle in a cardboard box. The bottle contains a silica gel desiccant container. This container must be left inside the bottle for the protection of the tablets and must not be swallowed.

Each box contains 30 or 90 (3 bottles of 30) film-coated tablets.

Only some packaging sizes may be marketed.

Darunavir Tarbis is also available in 400 mg and 600 mg film-coated tablets.

Marketing Authorization Holder and Responsible Manufacturer

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Responsible Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

PLA 3000 Paola

Malta

Amarox Pharma B.V.

Rouboslaan 32

2252 TR Voorschoten

Netherlands

This medicinal product is authorized in the 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 film-coated tablets

Last review date of this leaflet: March 2020.

For detailed and updated information on this medicinal product, please consult the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)