Package Leaflet: Information for the User

Darunavir Tarbis 600 mg Film-Coated Tablets EFG

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 they have the same symptoms as you, as it may harm them.
  
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. 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?

Darunavir Tarbis is used to treat adults and children aged 3 years or older and weighing at least 15 kilograms who are infected with HIV and have already used other antiretroviral medications.

Darunavir Tarbis should be taken with a low dose of 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 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 observe 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 it 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 taking 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 condition, including the duration of antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, and a higher body mass index. Signs of osteonecrosis include pain, discomfort, and stiffness in 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 or older. If you belong to this age group, please speak with your doctor to see if you can use this medication.

Children

Darunavir Tarbis is not used in children under 3 years of age or with a weight of less than 15 kilograms.

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 ritonavir with all protease inhibitors (PIs) and should not be used with other HIV protease inhibitors. In some cases, the dose of 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 problems) 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 inflammatory conditions, 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 condition called pulmonary hypertension)
• Glecaprevir/pibrentasvir, simeprevir(to treat hepatitis C infection)
• Fentanyl, oxycodone, tramadol(to treat pain)
• Fesoterodine, solifenacin(to treat urological disorders).

In certain cases, the dose of some medications may need to be adjusted as they may be affected by the combination, either by increasing the therapeutic or adverse effects of these or darunavir.

Inform your doctor if you take:

• Alfentanil(injection analgesic with strong and short action used in surgical procedures)
• Digoxin(to treat certain heart problems)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole can only be administered after a medical evaluation.
• Rifabutin(to treat bacterial infections)
• Sildenafil, vardenafil, tadalafil(for erectile dysfunction or high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone(to treat depression and anxiety)
• Maraviroc(to treat HIV infection)
• Methadone(to treat opioid dependence)
• Carbamazepine,clonazepam(to prevent seizures or treat certain types of neuropathic pain)
• Colchicine(to treat gout or familial Mediterranean fever)
• Bosentan(to treat high blood pressure in the pulmonary circulation)
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(to treat psychiatric conditions).

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 indicates it.Pregnant women orbreastfeeding 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 the 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 the 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 ritonavir without consulting your doctor, even if you feel better.

Once treatment has started, do not change the dose or form of the dose or interrupt treatment without consulting your doctor.

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

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

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

The dosage is:

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

• 800 mg of darunavir (2 400 mg darunavir tablets or 1 800 mg darunavir tablet) taken once a day with 100 mg of ritonavir. The 400 mg and 800 mg darunavir tablets are only used to obtain the 800 mg once-daily dosing regimen.

Please discuss with your doctor what dosage is correct for you.

Instructions for adults

• Take darunavir always with ritonavir. Darunavir does not act adequately without ritonavir.
• In the morning, take 1 600 mg darunavir tablet with 100 mg of ritonavir.
• In the evening, take 1 600 mg darunavir tablet with 100 mg of ritonavir.
• Take the tablets with food. Darunavir does not act adequately 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 potencies and as an oral suspension for patients who have difficulty swallowing.

Dosage for children aged 3 years or older, weighing at least 15 kg who have not taken antiretroviral medications before (will be determined by your child's doctor)

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

Your child's doctor will inform you about how many darunavir tablets and how much ritonavir (capsules, tablets or solution) your child should take.

oral solution of ritonavir: 80 mg per milliliter

Dosage for children aged 3 years or older, weighing at least 15 kg who have taken antiretroviral medications before (will be determined by your child's doctor)

Your child's doctor will establish the correct dose based on your child's weight (see table below). Your child's doctor will determine if the once-daily or twice-daily dose is appropriate for your child. This dose should not exceed the recommended adult dose, which is 600 mg of darunavir taken twice a day with 100 mg of ritonavir or 800 mg of darunavir taken once a day with 100 mg of ritonavir. Your child's doctor will inform you about how many darunavir tablets and how much ritonavir (capsules, tablets or solution) your child should take. Darunavir tablets in lower potencies are available to obtain the correct dosing regimen. The oral suspension of darunavir is also available. Your child's doctor will tell you if darunavir tablets or the oral suspension are suitable for your child.

Twice-daily dose

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

Once-daily dose

aoral solution of ritonavir: 80 mg per milliliter

Instructions for children

• Your child must take darunavir always with ritonavir. Darunavir cannot act adequately without ritonavir.
• Your child must take the correct dose of darunavir and ritonavir twice a day or once a day. If a twice-daily dose has been prescribed, your child must take one dose in the morning and one dose in the evening. Your child's doctor will determine the appropriate dosing regimen for your child.
• Your child must take darunavir with food. Darunavir cannot act adequately without food. The type of food is not important.
• Your child must swallow the tablets with a drink, such as water or milk.
• Darunavir is available in lower potencies and as an oral suspension for patients who have difficulty swallowing.

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 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 within6 hours, take the missed dose immediately. Always with ritonavir and with food. If you realizeafter 6 hours, omit that dose and continue with the usual dosing regimen. Do not take a double dose to compensate for the missed doses.

Do not stop taking Darunavir Tarbis without talking to your doctor

Antiretroviral 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.

Cases of liver problems have been reported, which may occasionally be severe. Your doctor will perform a blood test before you start 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 white of the eyes, darkening (tea color) of the urine, pale (movements of the intestine) stools, 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 experience 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)(can affect more than 1 in 10 patients)

• diarrhea.

Frequent 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, loss of strength, difficulty falling asleep.

Rare side effects (may affect up to 1 in 100 patients)(can 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, somnolence, depression, anxiety, abnormal dreams, decreased libido.

Rare side effects (may affect up to 1 in 1,000 patients)(can 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 discharge
• 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: an increase in 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 packaging and medications you no longer need at the SIGRE collection point at the pharmacy.Ask your pharmacist how to dispose of packaging and medications you no longer need if you are unsure. By doing so, you will help protect the environment.

Composition of Darunavir Tarbis 600 mg film-coated tablets EFG

• The active ingredient is darunavir. Each tablet contains 600 mg of darunavir.
• The other components are anhydrous colloidal silica (E551), microcrystalline cellulose silicified (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 packaging contents

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

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 60 film-coated tablets.

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

Sweden:Darunavir Amarox 600 mg Filmdragerade tabletter

Germany:Darunavir Amarox 600 mg Filmtabletten

Spain:Darunavir Tarbis 600 mg film-coated tablets EFG

Last review date of this leaflet:March 2020

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