DARUNAVIR VIVANTA 400 mg FILM-COATED TABLETS

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 40 kg body weight) who are infected with HIV and

• have not taken antiretroviral medicines before.
• have taken antiretroviral medicines before (as determined by your doctor).

This medicine must be taken with a low dose of ritonavir and other HIV medicines. 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 how serious your liver disease is. You may need to have some additional tests.

Tell your doctor about allthe medicines you are taking, including those you have bought from a pharmacy, supermarket or health food shop.

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 another 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 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 develop rash (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 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 previously not 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 upwards 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 taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to loss of blood supply to the bone). The risk of osteonecrosis is increased by long-term use of combination antiretroviral therapy, use of corticosteroids, long-term use of alcohol, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include pain, tenderness, and stiffness of the joints (especially the hip, knees, and shoulders) 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 and adolescents

This medicine should not be used in children under 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 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 inform your doctor and follow their instructions carefully 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 estrogen and hormone replacement therapy. Darunavir may reduce their effect. For birth control, alternative non-hormonal contraceptive 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 levels). 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 assessment and with close monitoring by your doctor to evaluate 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 as their effects, either therapeutic or adverse, may be altered when combined. Tell your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin(to reduce blood clotting)Alfentanil(a strong and short-acting injectable pain reliever used in surgical procedures)
• Digoxin(for the treatment of certain heart disorders)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole can only be administered after a medical evaluation.
• Rifabutin(against bacterial infections)
• Sildenafil, vardenafil, tadalafil(for erectile dysfunction or pulmonary arterial hypertension)
• 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 the treatment of gout or familial Mediterranean fever)
• Bosentan(for the treatment of pulmonary arterial hypertension)
• Buspirone, chlorazepate, 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 breastfeeding

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

Considering the potential adverse effects for the baby, women must not breastfeed their babies if they are taking darunavir.

It is recommended that HIV-infected women do not breastfeed their babies to avoid transmitting the HIV virus to them 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 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 should eat 30 minutes in advance. 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 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 from 3 years of age, weighing more than 40 kilograms, who have not taken antiretroviral medications before (to be determined by your child's doctor)

• The usual dose of darunavir is 800 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 from 3 years of age, weighing more than 40 kilograms, who have taken antiretroviral medications before (to be determined by your child's doctor)

The dose is:

• 800 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 from 3 years of age, 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 safety cap and is opened as follows:

• Push the plastic cap down, turning it counterclockwise at the same time.
• Remove the cap by unscrewing it.

If you take moreDarunavir Vivantathan you should

Inform your doctor, pharmacist, or nurse immediately.

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

If you forget to takeDarunavir 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 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 along 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 takingDarunavir Vivantawithout 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 suffer from them.

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

Cases of liver problems have been reported, which 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 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 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 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, belching, dry mouth, abdominal discomfort, constipation, burping
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• hives, severe skin and tissue swelling (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, 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: increased 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 is not listed 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 away through the sewers or in 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 400 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 side and "400" on the other.

Package size:

30 film-coated tablets or 60 film-coated tablets (2 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 600 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 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 400 mg film-coated tablets

Spain Darunavir Vivanta 400 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/