Darunavir Vivanta 800 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Darunavir Vivanta 800 mg film-coated tablets EFG

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, 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 these are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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, weighing at least 40 kilograms) infected with HIV and

• who have not previously used antiretroviral medicines, or
• in certain patients who have previously used antiretroviral medicines (this will be determined by your doctor).

This medicine must be taken together with a low dose of ritonavir and other anti-HIV medicines. Your doctor will advise you on the most suitable 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.

Medicine	Purpose of the medicine
Avanafil	treatment of erectile dysfunction
Astemizole or terfenadine	treatment of allergy symptoms
Triazolam and midazolam (oral)	to 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	to reduce 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 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 conditions 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 experience 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 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 anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections previously present without apparent symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you have started taking medicines for your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, ascending weakness starting in the hands and feet and moving toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive appropriate 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 receiving combination antiretroviral therapy may develop a bone condition called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Among the many risk factors for this condition are duration of combination antiretroviral therapy, corticosteroid use, 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.
• Inform your doctor if you are 65 years of age or older. 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 and adolescents

This medicine must not be used in children under 3 years of age or weighing less than 40 kilograms.

Taking Darunavir Vivanta with other medicines

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

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, it may be necessary to adjust the dose of other medicines. 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 take:

• 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 influence the effects of other medicines, and your doctor may want to perform additional blood tests. Inform your doctor if you take:

• 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 oestrogens and hormone replacement therapies. Darunavir may reduce their effectiveness. For birth control, non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most suitable cholesterol-lowering treatment based on your individual circumstances.
• Clarithromycin (an antibiotic).
• Cyclosporine, 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 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 alternatives cannot be used, their use should only occur after clinical evaluation and with close monitoring by your doctor to assess corticosteroid-related adverse effects.
• Buprenorphine/naloxone (medicines for opioid dependence treatment).
• Salmeterol (a medicine for asthma treatment).
• Artemether/lumefantrine (a combination of medicines to treat malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung 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 want to perform additional blood tests, and in certain cases, it may be necessary to adjust the dose of some medicines, as combining them may affect their therapeutic or adverse effects or those of darunavir. Inform your doctor if you take:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
• Alfentanil (a short-acting injectable strong painkiller used during surgical procedures)
• Digoxin (for the treatment of certain heart disorders)
• Clarithromycin (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 (to treat narcotic dependence)
• 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 when administered by injection, zolpidem (sedative agents)
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)
• Metformin (to treat type 2 diabetes)

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 should not take this medicine with ritonavir unless specifically instructed by their doctor. Pregnant women should not take this medicine with cobicistat.

Due to potential adverse effects on the infant, women should not breastfeed while receiving darunavir.

Breastfeeding is not recommended for women living with HIV 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 using 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 this 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.

After starting treatment, do not change the dose or dosing schedule or stop treatment without your doctor's instructions.

The 400-milligram darunavir tablets are only used to achieve the 800-milligram once-daily dosage regimen.

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

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

The usual dose of darunavir is 800 milligrams (2 tablets of 400 milligrams darunavir or 1 tablet containing 800 milligrams of darunavir) once daily.

You must 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. You should consume food 30 minutes before taking darunavir and ritonavir. The type of food is not important. Do not stop treatment with darunavir or ritonavir without first consulting your doctor, even if you feel better.

Instructions for adults

• Take two 400-milligram tablets at once, once daily, every day.
• Take darunavir always together with 100 milligrams of ritonavir.
• Take darunavir with food.
• Swallow the tablets or one 800 mg tablet with a drink, which may be water or milk.
• Take the other HIV medicines used in combination with darunavir and ritonavir as recommended by your doctor.
• The oral suspension of darunavir 100 milligrams per milliliter has been developed for use in children, but in some cases may also be used in adults.

Dosage for adults who have previously taken antiretroviral medicines (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) together with 100 milligrams of ritonavir once daily.

Or

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

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

Dosage for children aged 3 years and older, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (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) together with 100 milligrams of ritonavir once daily.

Dosage for children aged 3 years and older, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (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) together with 100 milligrams of ritonavir once daily.

Or

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

Please speak with 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 daily.
• Take darunavir always together with 100 milligrams of ritonavir.
• Take darunavir with food.
• Swallow the tablets with a liquid such as water or milk.
• Take the other medicines used in combination with darunavir and ritonavir as directed by your doctor.

Removing the child-resistant cap

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

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

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 at: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Darunavir Vivanta

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

If you vomit after taking darunavir and ritonavir

If you vomit within 4 hours after taking the medicine, you should take another dose of darunavir and ritonavir with some food as soon as possible. If you vomit more than 4 hours after taking the medicine, you do not 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 you miss a dose or vomit.

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

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

If you have any further 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 and lifestyle, and in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes.

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

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

Cases of liver problems have been reported, which occasionally may 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 or 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 common when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. A skin rash may also be a symptom of a rare but serious condition. Therefore, it is important to talk to your doctor if you develop a rash. Your doctor will advise you on how to manage the symptoms or whether darunavir should be discontinued.

Other serious adverse effects included diabetes (common) 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, drowsiness, 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, sore throat
• Stomach or mouth inflammation, heartburn, retching, dry mouth, abdominal discomfort, constipation, burping
• 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, herpes simplex
• Erectile dysfunction, breast enlargement
• Difficulty falling asleep, drowsiness, 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. In rare cases, these muscle disorders may be serious.

Reporting of adverse effects

If you experience any type of 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, after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must 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 in doubt, ask your pharmacist how to properly dispose of unused medicines and their packaging. 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 800 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 brown 85F565137 consisting of (poly)vinyl alcohol – partially hydrolyzed, titanium dioxide (E171), macrogol / PEG 3350, talc, iron oxide red (E172).

Appearance of Darunavir Vivanta and contents of the pack

Film-coated brown, oval-shaped, biconvex tablets, engraved with “D” on one side and “800” on the other.

Pack size:

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

Only certain pack sizes may be marketed.

Darunavir Vivanta is also available in 600 mg and 400 mg 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 further information about this medicinal product by contacting the local representative of the Marketing Authorization Holder:

Local Representative:

Vivanta Generics s.r.o. Spanish branch

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 800 mg Filmtabletten

Spain Darunavir Vivanta 800 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 for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/