Darunavir Vivanta 600 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Darunavir Vivanta 600 mg film-coated tablets EFG

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

What is Darunavir Vivanta?

This medicine contains the active substance darunavir. Darunavir is an antiretroviral medicine used in the treatment of 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. As a result, your immune system will improve and the risk of developing HIV-related illnesses will decrease.

What is it used for?

This medicine is used to treat adults and children aged 3 years and older who weigh at least 15 kilograms and who have been infected with HIV and have previously used other antiretroviral medicines.

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

Your doctor will advise you on the most appropriate combination of medicines for you.

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

Do not take Darunavir Vivanta

• if you are allergic to darunavir or to 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 unsure about the severity of your liver disease. Additional tests may be required.

Inform your doctor about all the medicines you are taking, including those taken orally, inhaled, injected, or applied to the skin.

Do not combine Darunavir Vivanta with any of the following medicines

If you are taking any of these drugs, consult your doctor to switch to another medicine.

Medication	Purpose of the medication
Avanafil	treatment of erectile dysfunction
Astemizole or terfenadine	treatment of allergy symptoms
Triazolam and midazolam (oral)	help you sleep and/or relieve anxiety
Cisapride	treatment of stomach problems
Colchicine (if you have kidney and/or liver problems)	treatment of gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	treatment of migraine-type headaches
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	treatment of certain cardiac conditions, for example irregular heartbeats
Lovastatin, simvastatin and lomitapide	lower cholesterol levels
Rifampicin	treatment of certain infections such as tuberculosis
The combination of lopinavir/ritonavir	this HIV medicine belongs to the same class as darunavir
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	treatment of enlarged prostate
Sildenafil	treatment of high blood pressure in the pulmonary circulation
Ticagrelor	to help prevent platelet aggregation in the treatment of patients with a history of heart attack
Naloxegol	to treat opioid-induced constipation
Dapoxetine	to treat premature ejaculation
Domperidone	to treat nausea and vomiting

Do not combine darunavir with products containing St. John's wort (Hypericum perforatum).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take this medicine.

This medicine does not cure HIV infection.

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

You must maintain regular contact with your doctor.

People taking darunavir may develop a skin rash. It is uncommon 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 develop rashes (usually mild or moderate) more frequently than patients taking either of these medicines separately.

Inform your doctor about your condition BEFORE and DURING your treatment

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

• Inform your doctor if you have had any liver disease, including hepatitis B or C infection. Your doctor will assess the severity of the liver disease before deciding whether you can take darunavir.
• Inform your doctor if you have diabetes. Darunavir may cause an increase in blood sugar levels.
• Inform your doctor immediately if you notice any signs of infection (e.g., 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 treatment for HIV. These symptoms are believed to result from an improved immune response, which enables the body to fight infections that were previously present without apparent symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition occurring when the immune system attacks healthy body tissue) may also occur after you have started taking medicines for the treatment of your HIV infection. Autoimmune disorders may appear many months after the start of treatment. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. Darunavir may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Inform your doctor if you notice any bone or muscle problems. Some patients using combined antiretroviral therapy may develop a bone disorder called osteonecrosis (death of bone tissue caused by reduced blood supply to the bone). Among the many risk factors for this condition are duration of combined antiretroviral therapy, use of corticosteroids, alcohol consumption, severe immunosuppression, and 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 see 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 speak with your doctor to determine whether you can use this medicine.

Children

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

Taking Darunavir Vivanta with other medicines

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

Some medicines must not be combined with 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 belonging to other classes [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested with all protease inhibitors (PIs) and must not be used with other HIV protease inhibitors. In some cases, the dose of other medicines may need to be changed. Therefore, if you are taking other anti-HIV medicines, always inform your doctor and follow their instructions carefully regarding which medicines can be combined.

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

• Phenobarbital, phenytoin (to prevent seizures)
• Dexamethasone (a corticosteroid)
• Efavirenz (for HIV infection)
• Rifapentine, rifabutin (medicines to treat certain infections such as tuberculosis)
• Saquinavir (for HIV infection).

Darunavir may also affect the effects of other medicines, and your doctor may wish to perform additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disorders), as the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), as the therapeutic or adverse effects of these medicines may be altered.
• Hormonal contraceptives based on oestrogens and hormone replacement therapies. Darunavir may reduce their effectiveness. For contraception, non-hormonal alternative methods are recommended.
• Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels caused by drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most appropriate cholesterol-lowering treatment based on your individual circumstances.
• Clarithromycin (an antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), as 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 diseases, inflammatory skin, eye, joint, and muscle conditions, and other inflammatory disorders. These medicines are usually taken orally, inhaled, injected, or applied to the skin. If no alternatives are available, their use should only occur after clinical evaluation and with close monitoring by your doctor for corticosteroid-related adverse effects.
• Buprenorphine/naloxone (medicines for opioid dependence treatment)
• Salmeterol (a medicine for asthma treatment)
• Artemether/lumefantrine (a combination of medicines for treating malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (for treating cancer)
• 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 (to treat pain)
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may wish to perform additional blood tests, and in certain cases, it may be necessary to adjust the dose of some medicines, as their therapeutic or adverse effects, or those of darunavir, may be affected when combined. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting). Alfentanil (a short-acting, potent injectable analgesic used in surgical procedures).
• Digoxin (for the treatment of certain heart disorders).
• Claritromycin (an antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be administered after medical evaluation.
• Rifabutin (for bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety).
• Maraviroc (to treat HIV infection).
• Methadone (for narcotic dependence treatment).
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain).
• Colchicine (for the treatment of gout or familial Mediterranean fever).
• Bosentan (for the treatment of high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem (sedative agents).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Taking Darunavir Vivanta with food and drinks

See section 3 “How to take Darunavir Vivanta.”

Pregnancy and breastfeeding

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

Due to possible adverse effects on the infant, women must not breastfeed while receiving darunavir.

Women living with HIV are not advised to breastfeed because HIV infection can be transmitted to the baby through breast milk. If you are breastfeeding or considering breastfeeding, you should consult your doctor as soon as possible.

Driving and use of machines

Do not operate tools or machinery or drive 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, i.e., essentially "sodium-free".

3. How to take Darunavir Vivanta

Follow exactly the dosing instructions for the medicine provided in this leaflet or those given by your doctor, pharmacist, or nurse. If in doubt, ask your doctor, pharmacist, or nurse.

Do not stop taking this medicine or ritonavir without first consulting your doctor, even if you feel better.

Once treatment has been started, the dose or dosing regimen should not be changed or treatment interrupted without consulting your doctor.

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

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

Dosage for adults who have previously taken antiretroviral medicines (to be determined by your doctor)

The dose is:

• 600 milligrams of darunavir together with 100 milligrams of ritonavir twice daily.

Or

• 800 milligrams of darunavir (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) together with 100 milligrams of ritonavir once daily. The 400-milligram and 800-milligram darunavir tablets are only used to achieve the 800-milligram once-daily dosing regimen.

Please speak with your doctor about which dose is correct for you.

Instructions for adults

• Always take this medicine with ritonavir. Darunavir does not work properly without ritonavir.
• In the morning, take one 600-milligram tablet of this medicine together with 100 milligrams of ritonavir.
• In the evening, take one 600-milligram tablet of this medicine together 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 may be water or milk.

Dosage for children aged 3 years and older, weighing at least 15 kilograms, who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

The doctor will calculate the correct daily dose based on the child's body weight (see table below). This dose must not exceed the recommended adult dose, which is 800 milligrams of darunavir together with 100 milligrams of ritonavir once daily.

Your doctor will inform you about the amount of darunavir tablets and the amount of ritonavir (capsules, tablets, or solution) the child should take.

Weight	A dose of darunavir is	A dose of ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
over 40 kilograms	800 milligrams	100 milligrams

Ritonavir oral solution: 80 milligrams per millilitre

Dosage for children aged 3 years and older, weighing at least 15 kilograms, who have previously taken antiretroviral medicines (your child's doctor will determine this)

The correct dose will be established by the doctor according to the child's weight (see table below). The doctor will decide whether a once-daily or twice-daily dosing regimen is appropriate for the child. This dose must not exceed the recommended adult dose, which is 600 milligrams of darunavir together with 100 milligrams of ritonavir twice daily, or 800 milligrams of darunavir together with 100 milligrams of ritonavir once daily. Your doctor will inform you how many darunavir tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Lower-strength tablets are available to achieve the appropriate dosing schedule. Darunavir oral suspension is also available (marketed by various marketing authorization holders). Your doctor will advise whether darunavir tablets or oral suspension are suitable for the child.

Twice-daily dosing

Weight	One dose is
between 15 and 30 kilograms	375 milligrams of darunavir + 50 milligrams of ritonavir twice daily
between 30 and 40 kilograms	450 milligrams of darunavir + 60 milligrams of ritonavir twice daily
over 40 kilograms*	600 milligrams of darunavir + 100 milligrams of ritonavir twice daily

• The doctor will determine whether the 800 mg once-daily dose can be used for children 12 years of age and older and weighing at least 40 kilograms. This dose cannot be administered with the 600 mg tablets. Other darunavir formulations are available.

Once-daily dosing

Weight	A dose of darunavir is	A dose of ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
more than 40 kilograms	800 milligrams	100 milligrams

ritonavir oral solution: 80 milligrams per milliliter

Instructions for children

• The child must always take darunavir together with ritonavir. Darunavir cannot work properly without ritonavir.
• The child must take the correct dose of darunavir and ritonavir twice daily or once daily, as prescribed. If darunavir has been prescribed twice daily, the child should take one dose in the morning and one in the evening. Your child's doctor will determine the appropriate dosing schedule for your child.
• The child must take darunavir with food. Darunavir cannot work properly without food. The type of food does not matter.
• The child should swallow the tablets with a drink such as water or milk.

Removing the child-resistant cap

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

• • Press down on the plastic cap while turning it counterclockwise.
• • Unscrew and remove the cap.

If you take more Darunavir Vivanta than you should

Contact your doctor, pharmacist, or nurse immediately.

In case of overdose or accidental ingestion, go to a medical center or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medication and the amount taken.

If you forget to take Darunavir Vivanta

If you realize within 6 hours, take the missed dose immediately, always with ritonavir and with food. If you realize after 6 hours, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a missed dose.

If the child vomits after taking Darunavir Vivanta and ritonavir

If vomiting occurs within 4 hours after taking the medicine, another dose of darunavir and ritonavir should be taken with some food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, there is no need to take another dose of darunavir and ritonavir until the next scheduled dose.

Contact your doctor if you have any doubts about what to do if a dose is missed or if vomiting occurs.

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

HIV medicines may make you feel better. However, even if you feel better, do not stop taking darunavir. Always consult your doctor first.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

Cases of liver problems have been reported, which may occasionally be serious. 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 you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin and whites of the eyes, darkening (tea-colored) of the urine, pale-colored stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under your ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. However, a skin rash can also be a symptom of a rare but serious condition. Therefore, it is important to speak with your doctor if you develop a rash. Your doctor will advise you on how to manage symptoms or whether darunavir should be discontinued.

Other serious adverse effects include diabetes (frequent) and inflammation of the pancreas (uncommon).

Very common adverse effects (may affect more than 1 in 10 patients)

• Diarrhea

Common adverse effects (may affect up to 1 in 10 patients)

• Vomiting, nausea, abdominal pain or bloating, upper abdominal pain (dyspepsia), flatulence
• Headache, fatigue, dizziness, somnolence, numbness, tingling, or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon adverse effects (may affect up to 1 in 100 patients)

• Chest pain, changes in electrocardiogram, rapid heartbeat
• Decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance
• Difficulty breathing, cough, nosebleed, 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 lips or eyes), eczema, excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration
• Muscle pain, muscle cramps or weakness, limb pain, osteoporosis
• Reduced thyroid gland function. This can be seen in a blood test.
• Hypertension (increased blood pressure), flushing
• Red or dry eyes
• Fever, swelling of the lower limbs due to fluid retention, malaise, irritability, pain
• Symptoms of infection, simple herpes
• Erectile dysfunction, breast enlargement
• Difficulty falling asleep, somnolence, depression, anxiety, abnormal dreams, decreased sex drive

Rare adverse effects (may affect up to 1 in 1,000 patients)

• A reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage]
• Myocardial infarction, slow heartbeat, palpitations
• Visual disturbance
• Chills, unusual 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 or joint stiffness, joint pain with or without inflammation
• Changes in certain 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 certain white blood cells
• Darunavir crystals in the kidney causing kidney disease

Some adverse effects are typical of HIV medicines belonging to the same class as darunavir. These include:

• Muscle pain, tenderness, or weakness. Rarely, these muscle disorders may be serious.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide 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 expiry date stated on the carton and on the bottle, following EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Darunavir Vivanta

• The active substance is darunavir. Each tablet contains 600 milligrams of darunavir.

• The other components are:

• Tablet core: Silicified microcrystalline cellulose (microcrystalline cellulose + colloidal anhydrous silica), crospovidone B, hydroxypropylcellulose, sodium chloride, colloidal anhydrous silica, magnesium stearate and polacriline potassium.

• Coating: Opadry II beige 85F570070 consisting of (poly) vinyl alcohol - partially hydrolysed, titanium dioxide (E171), macrogol / PEG 3350, talc, yellow iron oxide (E172), red iron oxide (E172).

Appearance of Darunavir Vivanta and contents of the pack

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

Pack sizes:

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 child-resistant closure.

Only certain pack sizes may be commercially available.

Darunavir Vivanta is also available as 400 mg and 800 mg film-coated tablets.

Marketing Authorization Holder

Vivanta Generics s.r.o.

Trtinová 260/1, Cakovice

196 00 Prague 9

Czech Republic

Manufacturer responsible

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park,

Paola, PLA3000,

Malta

You can request further information about this medicinal product 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, edificio Britannia

28003 Madrid

Spain

This medicinal product is authorized in the European Economic Area member states under the following names:

Germany Darunavir Vivanta 600 mg Filmtabletten

Spain Darunavir Vivanta 600 mg film-coated tablets EFG

Date of the most recent revision of this leaflet: May 2023

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