DARUNAVIR VIVANTA 800 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Darunavir Vivanta 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 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. Storage of 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 Human Immunodeficiency Virus (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 reduces the risk of developing the illnesses that people with HIV get.

What is it used for?

This medicine is used to treat adults and children (from 3 years of age and at least 40 kg body weight) who are infected with HIV and

• have not taken antiretroviral medicines before.
• have taken antiretroviral medicines before (your doctor will determine this).

This medicine must be taken in combination with other HIV medicines and with a low dose of ritonavir. Your doctor will discuss with you which combination of medicines is best for 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 what your liver condition is. You may need to have some blood tests to check your liver.

Tell your doctor about allthe medicines you are taking, including those you have bought without a prescription, herbal remedies, and those you have been given by your doctor.

Do not take Darunavir Vivanta with any of the following medicines

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

Do not take 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 infections or other illnesses associated with HIV.

You must remain under the care of your doctor while taking this medicine.

People taking darunavir may develop a skin rash. This is not common but can be severe or potentially life-threatening. Please consult your doctor if you develop a rash.

Patients taking darunavir and raltegravir (for HIV infection) may develop rashes (usually mild or moderate) more often 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 ever had liver disease, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding if 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 the body to fight off these infections.
• 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 to receive necessary treatment.
• Tell your doctor if you have hemophilia. Darunavir may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides(for example, used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of time you are taking combination antiretroviral therapy, the use of corticosteroids, drinking alcohol, being overweight, and having a low bone density can increase the risk of developing osteonecrosis. Signs of osteonecrosis include joint pain or pain in your arms or legs, joint stiffness, 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

This medicine must not be used in children below 3 years of age or weighing less than 40 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 takenwith this medicine. The list can be found in the section “Do not take Darunavir Vivanta with any of the following medicines”

In most cases, darunavir can be taken with other anti-HIV medicines that belong to 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 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 tell your doctor and carefully follow their instructions on which medicines can be taken together.

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 conditions) 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 birth control, 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 decide which treatment to lower your cholesterol 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 diseases, and other inflammatory diseases. These medicines are usually taken by mouth, inhaled, injected, or applied to the skin. If alternatives cannot be used, their use should only be done after a clinical assessment 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(to treat hepatitis C infection).
• 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 they may affect the therapeutic or adverse effects of these or of darunavir. Tell your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin(to reduce blood clotting)
• Alfentanil(a strong, short-acting injectable pain reliever used in surgical procedures)
• Digoxin(for the treatment of certain heart conditions)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole can only be given after a medical assessment.
• 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)
• Maraviroc(for HIV infection treatment)
• Methadone(for narcotic dependence treatment)
• Carbamazepine, clonazepam(to prevent seizures or to treat certain types of neuropathic pain)
• Colchicine(for gout or familial Mediterranean fever treatment)
• Bosentan(for high blood pressure in the pulmonary circulation treatment)
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when given by injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(for psychiatric conditions treatment)
• Metformin(for type 2 diabetes 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 breast-feeding

Tell your doctor immediately if you are pregnant or are planning to become pregnant. Pregnant women should not take this medicine with ritonavir unless specifically advised by their doctor. Pregnant women should not take this medicine with cobicistat.

Considering the potential adverse effects for the baby, women should not breast-feed while taking darunavir.

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

Driving and using machines

Do not drive or operate machinery if you experience dizziness 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 for this medication 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 medication 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.

The 400-milligram darunavir tablets are used only to obtain the 800-milligram dosage once a day.

The 800-milligram darunavir tablets are intended for daily use only.

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

The normal dose of darunavir is 800 milligrams (2 tablets of 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) once a day.

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

Instructions for Adults

• Take two 400-milligram tablets at the same time, once a day, every day.
• Always take darunavir with 100 milligrams of ritonavir.
• Take darunavir with food.
• Swallow the tablets or an 800-mg tablet with a drink that can be water or milk.
• Take the other HIV medications used in combination with darunavir and ritonavir as your doctor recommends.
• The 100 milligrams per milliliter oral suspension of darunavir has been developed for use in children, but in some cases, it can also be used in adults.

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

The dose is:

• 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.

Or

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

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

Dose for Children Aged 3 Years and Older, 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 milligrams (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) along with 100 milligrams of ritonavir once a day.

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

The dose is:

• 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.

Or

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

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

Instructions for Children Aged 3 Years and Older, Weighing More Than 40 Kilograms

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

Removing the Child-Resistant Cap

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

• Push the plastic cap down, turning it counterclockwise at the same time.
• 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 medication and the amount used.

If You Forget to Take Darunavir Vivanta

If you realize within 12 hours, take the tablets immediately. Always take the dose with ritonavir and with food. If you realize after 12 hours, skip that dose and make the next one in the usual way. Do not take a double dose to make up for the forgotten doses.

If You Vomit After Taking Darunavir and Ritonavir

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

Contact your doctor if you 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 medications can make you feel better. Even if you feel better, do not stop taking darunavir. 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 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 may include yellowing of the skin and the whites of the eyes, darkening (tea color) of the urine, pale stools (intestinal movements), nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness on 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 serious situation. Therefore, it is essential to talk to your doctor if you present a rash. Your doctor will advise you on how to control the symptoms or if you should interrupt 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, pain in the upper abdomen (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, belching, 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), damage to the liver, kidney, or lung]
• myocardial infarction, slow heart rate, palpitations
• visual impairment
• chills, strange sensation
• a feeling of confusion or disorientation, altered mood, agitation
• fainting, epileptic seizure, changes or loss of taste
• mouth ulcers, vomiting blood, lip inflammation, dry lips, tongue with thrush
• nasal discharge
• skin lesions, dry skin
• muscle stiffness or joint pain, joint pain with or without inflammation
• changes in some blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: increase in some white blood cells
• darunavir crystals in the kidney that cause kidney disease.

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 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 Medication Pharmacovigilance System for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Darunavir Vivanta

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the bottle, after CAD. The expiration date is 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 containers and medications you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the containers and medications 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 800 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 polacrylate.
• Coating: Opadry II brown 85F565137, which consists of (poly)vinyl alcohol - partially hydrolyzed, titanium dioxide (E171), macrogol/PEG 3350, talc, and iron oxide red (E172).

Appearance of Darunavir Vivanta and Package Contents

Film-coated tablets of brown color, oval shape, biconvex, engraved with "D" on one side and "800" on the other.

Package size:

30 film-coated tablets or 90 film-coated tablets (3 bottles containing 30 tablets each) in an HDPE bottle with a child-resistant closure.

Only some package sizes may be marketed.

Darunavir Vivanta is also available in 600-milligram and 400-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 medication 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 medication is authorized in the Member States of the European Economic Area with the following names:

Germany Darunavir Vivanta 800 mg film-coated tablets

Spain Darunavir Vivanta 800 mg film-coated tablets EFG

Date of the last revision of this prospectus: May 2023

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