DARUNAVIR VIVANTA 600 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

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

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

What is Darunavir Vivanta?

This medicine contains the active substance darunavir. Darunavir is an antiretroviral medicine used to treat HIV infection. It belongs to a group of medicines called protease inhibitors. This medicine reduces the amount of HIV in your body. This means that your immune system should improve and reduce the risk of developing illnesses associated with HIV infection.

What is it used for?

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

This medicine must be taken with a low dose of ritonavir and other HIV medicines.

Your doctor will discuss the most suitable combination of medicines with you.

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

Do not take Darunavir Vivanta

• 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.

Tell your doctor about allthe medicines you are taking, including those you bought without a prescription, herbal remedies, and those you are taking for other health problems.

Do not combine Darunavir Vivanta 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 darunavir with products that contain St. John's Wort (Hypericum perforatum).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before you start taking this medicine.

This medicine does not cure HIV infection.

People taking darunavir may still develop other infections and diseases associated with HIV infection.

You must keep in regular contact with your doctor.

People taking darunavir may develop a 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 be more likely to develop rash (usually mild or moderate) than patients taking either of these medicines separately.

Tell your doctor about your situation BEFORE and DURING treatment

Make sure you check the following points and tell your doctor if any of them apply to you.

• Tell your doctor if you have had liver disease, including infection with hepatitis B or C. Your doctor will assess the severity of your liver disease before deciding whether you can take darunavir.
• 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 and fever). In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body's immune response, enabling it to fight off infections that 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 start taking medicines for your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness that starts in the hands and feet and moves up towards the trunk of the body, palpitations, tremor, or hyperactivity, inform your doctor immediately for 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 due to lack of blood supply to the bone). The risk of osteonecrosis is increased by the use of corticosteroids, prolonged use of antiretroviral therapy, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include pain, tenderness, and swelling 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

This medicine should not be used in children under 3 years of age or weighing less than 15 kg.

Taking Darunavir Vivanta 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 Vivanta 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 ritonavir and all protease inhibitors (PIs) 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 inform your doctor and carefully follow their instructions 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)
• Rifapentine, rifabutin(medicines to treat certain infections such as tuberculosis)
• Saquinavir(for HIV infection).

Darunavir may also affect the action of other medicines, and your doctor may need to do some additional blood tests. 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, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel(to reduce blood clotting) because the therapeutic or adverse effects of these medicines may be altered.
• Hormonal contraceptives based on estrogens and hormone replacement therapy. Darunavir may reduce their effectiveness. For contraception, alternative non-hormonal 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 best for you based on your personal circumstances.
• Clarithromycin(antibiotic)
• Ciclosporin, everolimus, tacrolimus, sirolimus(to suppress the immune system) because the therapeutic or adverse effects of these medicines may be increased.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel disease, inflammatory skin, eye, joint, and muscle disorders, and other inflammatory conditions. These medicines are usually taken orally, inhaled, injected, or applied to the skin. 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 pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir(for hepatitis C infection treatment)
• Fentanyl, oxycodone, tramadol(for pain treatment)
• Fesoterodine, solifenacin(for urological disorders treatment).

Your doctor may need to do some additional blood tests and in certain cases, it may be necessary to adjust the dose of some medicines because when combined, the therapeutic or adverse effects of these or darunavir may be affected. Tell your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin(to reduce blood clotting). Alfentanil(injectable analgesic with strong and short action used in surgical procedures).
• Digoxin(for certain heart disorders treatment).
• 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 pulmonary arterial hypertension).
• 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 gout or familial Mediterranean fever treatment).
• Bosentan(for pulmonary arterial hypertension treatment).
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem(sedative agents).
• 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 Vivanta with food and drink

See section 3 "How to take Darunavir Vivanta."

Pregnancy and breastfeeding

Tell your doctor immediately if you are pregnant or plan to become pregnant. Pregnant women should not take this medicine with ritonavir unless their doctor specifically instructs them to do so. Pregnant women should not take this medicine with cobicistat.

Considering the potential side effects for the baby, women should not breastfeed their children if they are taking darunavir.

It is not recommended that HIV-infected women breastfeed their babies because HIV can be transmitted through breast milk. If you are breastfeeding or thinking of breastfeeding, consult your doctor as soon as possible.

Driving and using machines

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

Darunavir Vivanta contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet, which is essentially "sodium-free".

3. How to take Darunavir Vivanta

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 this medicine 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 a doctor.

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

You will need a different dose of this medicine that cannot be administered with these 600-milligram tablets. Other concentrations of this medicine are available.

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

The dose is:

• 600 milligrams of darunavir along with 100 milligrams of ritonavir twice a day.

Or

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

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

Instructions for adults

• Take this medicine always along with ritonavir. Darunavir does not work properly without ritonavir.
• In the morning, take one 600-milligram tablet of this medicine along with 100 milligrams of ritonavir.
• In the evening, take one 600-milligram tablet of this medicine along with 100 milligrams of ritonavir.
• Take this medicine 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.

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

The doctor will calculate the correct daily dose based on the child's weight (see 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 ritonavir solution: 80 milligrams per milliliter

Dose for children from 3 years of age, with at least 15 kilograms of weight who have taken antiretroviral medicines before (to be determined by the 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 appropriate 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 concentration tablets are available to achieve the appropriate dose. The oral suspension of darunavir (marketed by different marketing authorization holders) is also available. Your doctor will tell you if the darunavir tablets or the oral suspension are suitable for the child.

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 darunavir presentations are available.

Dose once a day

Oral ritonavir solution: 80 milligrams per milliliter

Instructions for children

• The child must take darunavir always along with ritonavir. Darunavir cannot work properly without ritonavir.
• The child must take the correct dose of darunavir and ritonavir twice a day or once a day. If darunavir is prescribed twice a day, the child must 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 must take darunavir with food. Darunavir cannot work properly without food. The type of food is not important.
• The child must swallow the tablets with a drink, which can be water or milk.

Child-resistant cap removal

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

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

If you take more Darunavir Vivanta than you should

Inform your doctor, pharmacist, or nurse immediately.

In case of overdose or accidental ingestion, go to a medical center or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount used.

If you forget to take Darunavir Vivanta

If you realize within 6 hours, take the forgotten dose immediately. Always with ritonavir and with food. If you realize after 6 hours, skip that dose and do the next one as usual. Do not take a double dose to make up for forgotten doses.

If you vomit after taking Darunavir Vivanta and ritonavir

If you vomit within 4 hoursafter taking the medicine, you should take another dose of darunavir and ritonavir along with some food as soon as possible. If you vomit when more than 4 hourshave passed since you took the medicine, it is not necessary to take another dose of darunavir and ritonavir until the next scheduled administration time.

Contact your doctor ifyou have doubtsabout what to do if you forget a dose or vomit.

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

HIV medicines can make you feel better. Even if you feel better, do not stop taking darunavir. Consult your doctor first.

If you have any other doubts about the use of this medicine, 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 medicines themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause side effects, although not everybody gets 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 you start 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 greater likelihood of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These can include yellowing of the skin and the whites of the eyes, darkening (tea color) of the urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, feeling of pain or discomfort 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 important that you talk to your doctor if you present a rash. Your doctor will advise you on how to control the symptoms or if you should stop 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, 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, coated tongue
• 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: increase in some white blood cells
• darunavir crystals in the kidney that cause kidney disease.

Some side effects are typical of HIV medicines 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 of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Darunavir Vivanta

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

Do not use this medicine after the expiration date that appears on the box and on the bottle, after EXP. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines that you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Darunavir Vivanta

• The active ingredient is darunavir. Each tablet contains 600 milligrams of darunavir.
• The other ingredients are:

• Core of the tablet: Silicified microcrystalline cellulose (microcrystalline cellulose + anhydrous colloidal silica), crospovidone B, hydroxypropylcellulose, sodium chloride, anhydrous colloidal silica, magnesium stearate, and potassium polacrilin.
• Coating: Opadry II beige 85F570070, which consists of [(poly)vinyl alcohol-partially hydrolyzed], titanium dioxide (E171), macrogol/PEG 3350, talc, yellow iron oxide (E172), red iron oxide (E172).

Appearance of Darunavir Vivanta and package contents

Beige film-coated tablets, oval, biconvex, engraved with "D" on one face and "600" on the other.

Package size:

30 film-coated tablets, 60 film-coated tablets (2 bottles containing 30 tablets each) or 180 film-coated tablets (6 bottles containing 30 tablets each) in an HDPE bottle with a child-resistant cap.

Only some package sizes may be marketed.

Darunavir Vivanta is also available in 400-milligram and 800-milligram film-coated tablets.

Marketing authorization holder

Vivanta Generics s.r.o.

Trtinová 260/1, Cakovice

196 00 Prague 9

Czech Republic

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park,

Paola, PLA3000,

Malta

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Local representative:

Vivanta Generics s.r.o. branch in Spain

C/Guzmán el Bueno, 133, Britannia building

28003 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area with the following names:

Germany Darunavir Vivanta 600 mg film-coated tablets

Spain Darunavir Vivanta 600 mg film-coated tablets EFG

Date of the last revision of this prospectus: May 2023

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