DARUNAVIR AUROVITAS 800 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

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

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

What is Darunavir Aurovitas?

Darunavir Aurovitas 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. Darunavir reduces the amount of HIV in your body. This improves your immune system and reduces the risk of developing illnesses associated with HIV infection.

What is it used for?

The 800-milligram darunavir tablet is used to treat adults and children (from 3 years of age and at least 40 kilograms in weight) infected with HIV and:

• who have not taken antiretroviral medicines before.
• in certain patients who have taken antiretroviral medicines before (as determined by your doctor).

Darunavir must be taken with a low dose of cobicistat or ritonavir and other HIV medicines. Your doctor will discuss the most suitable combination of medicines with you.

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

Do not take Darunavir Aurovitas

• If you are allergic to darunavir or any of the other ingredients of this medicine (listed in section 6) or to cobicistat or ritonavir.
• If you have severe liver problems. Ask your doctor if you are not sure about the severity of your liver disease. You may need to have some additional tests.

Tell your doctor about allthe medicines you are taking, including those you are taking orally, inhaled, injected, or applied to the skin.

Do not combine darunavir with any of the following medicines

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

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before you start taking Darunavir Aurovitas.

Darunavir does not cure HIV infection.

People taking darunavir may develop other infections or diseases associated with HIV infection. You must remain under regular medical care.

People taking darunavir may develop a skin rash. It is not common for the rash to be severe or life-threatening. 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 the two medicines separately.

Tell your doctor about your situation BEFORE and DURING your treatment

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

• Tell your doctor if you have had any 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 (e.g., swollen lymph nodes, 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 soon after starting HIV treatment. These symptoms are thought to be due to an improvement in the body's immune response, enabling it to fight off infections that were not apparent before.
• In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you have started taking medicines for the treatment of your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up towards the trunk of the body, palpitations, tremor, or hyperactivity, tell your doctor immediately to receive 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 (e.g., used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients using combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to lack of blood supply to the bone). Many factors can increase the risk of developing this disease, including long-term use of combination antiretroviral therapy, use of corticosteroids, alcohol consumption, severe immune suppression, and higher body mass index. Signs of osteonecrosis are pain, discomfort, and stiffness of the joints (especially the hip, knee, and shoulder) 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, consult your doctor to see if you can use darunavir.

Children and adolescents

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

Other medicines and Darunavir Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Some medicines must not be combinedwith darunavir. The list can be found in the section “Do not combine darunavir 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 has not been tested with cobicistat or ritonavir and all protease inhibitors (PIs) and must not be used with other HIV protease inhibitors. In some cases, it may be necessary to change the dose of the other medicines. Therefore, if you are taking other anti-HIV medicines, always inform your doctor and carefully follow their instructions on which medicines can be combined.

The following products may reduce the effectiveness 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 effects of other medicines, and your doctor may want to do some additional blood tests. Tell your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disorders) because the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting) because the therapeutic or adverse effects of these medicines may be altered.
• Hormonal contraceptives based on estrogens and hormone replacement therapy. Darunavir may reduce their effectiveness. For 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). There may be an increased risk of muscle damage. Your doctor will determine which cholesterol-lowering treatment is most suitable for you based on your personal circumstances.
• Clarithromycin (antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system) because the therapeutic or adverse effects of these medicines may be increased. Your doctor may do some additional tests.
• 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 disorders, and other inflammatory conditions. These medicines are usually taken orally, inhaled, injected, or applied to the skin. If alternatives cannot be used, their use should only be done after a clinical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.
• Buprenorphine/naloxone (medicines for opioid dependence treatment).
• Salmeterol (medicine for asthma treatment).
• Artemether/lumefantrine (a combination of medicines to treat malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (for cancer treatment).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or 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 want to do some additional blood tests, and in certain cases, it may be necessary to modify the dose of some medicines since their therapeutic or adverse effects may be affected 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 treatment).
• Maraviroc (for HIV infection treatment).
• Methadone (for opioid 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 pulmonary arterial hypertension treatment).
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, midazolam administered 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 Aurovitas with food and drinks

See section 3 “How to take Darunavir Aurovitas”.

Pregnancy and breastfeeding

Tell your doctor immediately if you are pregnant, plan to become pregnant, or are breastfeeding. Pregnant women must not take darunavir with ritonavir unless their doctor specifically instructs them to do so. Pregnant women must not take darunavir with cobicistat.

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

It is not recommended that women living with HIV breastfeed their babies because HIV infection can be passed to the baby 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 darunavir.

Darunavir Aurovitas contains propylene glycol

This medicine contains 111.12 mg of propylene glycol in each film-coated tablet. If the baby is less than 4 weeks old, consult your doctor or pharmacist, especially if the baby has been given other medicines that contain propylene glycol or alcohol.

3. How to take Darunavir Aurovitas

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

Once treatment has started, the dose or form of the dose should not be changed or treatment interrupted without consulting the doctor.

The 800 milligram darunavir tablets are used only for the 800 milligram once-daily regimen.

This product is only available in film-coated tablet form and is therefore not suitable for patients who cannot swallow whole tablets, for example, young children. For use in these patients, the availability of darunavir in a more suitable formulation should be checked.

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

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

You should take darunavir every day and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. Darunavir does not work properly without cobicistat or ritonavir and food. Before taking darunavir and cobicistat or ritonavir, you should eat 30 minutes before. The type of food is not important. Do not interrupt treatment with darunavir or cobicistat or ritonavir without consulting your doctor first, even if you feel better.

Instructions for adults

• Take one 800 milligram darunavir tablet at the same time, once a day, every day.
• Always take darunavir with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take darunavir with food.
• Swallow the tablets with a drink, which can be water or milk.
• Take the other HIV medications used in combination with darunavir and cobicistat or ritonavir as your doctor recommends.

Dose for adults who have taken antiretroviral medications before (will be determined by your doctor)

You may require a different dose of darunavir that cannot be administered with these 800 milligram tablets. Other doses of darunavir are available.

The dose is:

• 800 milligrams of darunavir (1 tablet containing 800 milligrams of darunavir) with 150 milligrams of cobicistat or 100 milligrams of ritonavir once a day.

Or

• 600 milligrams of darunavir (1 tablet containing 600 milligrams of darunavir) with 100 milligrams of ritonavir twice a day.

Talk to your doctor about which dose is correct for you.

Dose for children from 3 years of agewith ritonavir and from 12 years of age with cobicistat, who weigh more than 40 kilograms, who have not taken antiretroviral medications before (will be determined by your child's doctor)

• The usual dose of darunavir is 800 milligrams (1 tablet containing 800 milligrams of darunavir) with 100 milligrams of ritonavir or 150 milligrams of cobicistat once a day.

Dose for children from 3 years of agewith ritonavir and from 12 years of age with cobicistat, who weigh more than 40 kilograms, who have taken antiretroviral medications before (will be determined by your child's doctor)

The dose is:

• 800 milligrams of darunavir (1 tablet containing 800 milligrams of darunavir) with 100 milligrams of ritonavir or 150 milligrams of cobicistat once a day.

Or

• 600 milligrams of darunavir (1 tablet containing 600 milligrams of darunavir) with 100 milligrams of ritonavir twice a day.

Talk to your doctor about which dose is correct for you.

Instructions for children from 3 years of agewith ritonavir and from 12 years of age with cobicistat, who weigh more than 40 kilograms

• Take 800 milligrams of darunavir (1 tablet containing 800 milligrams of darunavir) at the same time, once a day, every day.
• Always take darunavir with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
• Take darunavir with food.
• Swallow the tablets with a liquid such as water or milk.
• Take the other HIV medications used in combination with darunavir and ritonavir or cobicistat as your doctor recommends.

Child-resistant cap removal

If you take moreDarunavir Aurovitasthan you should

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or nurse immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to takeDarunavir Aurovitas

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

If you vomit after taking darunavir and cobicistat or ritonavir

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

Contact your doctor if you have doubts about what to do if you forget a dose or vomit.

Do not stop takingDarunavir Aurovitaswithout 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 the 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:

Cases of liver problems have been reported, which can occasionally be severe. Your doctor will perform a blood test before starting treatment with darunavir. If you have a chronic infection caused by hepatitis B or C, your doctor will check your blood tests more frequently, 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-colored stools (bowel movements), nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness 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 interrupt darunavir.

Other serious side effects were diabetes (frequent) and pancreatitis (uncommon).

Very common(may affect more than 1 in 10 people)

• Diarrhea.

Common(may affect up to 1 in 10 people)

• Vomiting, nausea, abdominal pain or distension, upper abdominal pain (dyspepsia), flatulence.
• Headache, fatigue, dizziness, drowsiness, numbness, tingling, or pain in the hands or feet, loss of strength, difficulty staying asleep.

Uncommon(may affect up to 1 in 100 people)

• Chest pain, changes in the electrocardiogram, rapid heart rate.
• 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 the lips or eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail discoloration.
• Muscle pain, sensitivity, or weakness. In rare cases, these muscle disorders can be severe.
• 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, herpes simplex.
• Erectile dysfunction, breast enlargement.
• Sleep disorders, drowsiness, depression, anxiety, abnormal dreams, decreased sexual desire.

Rare(may affect up to 1 in 1,000 people)

• A reaction called DRESS [severe rash, which can 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 disturbance.
• 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 or joint stiffness, 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, which 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 leaflet. You can also report them directly through the Spanish Medicines Agency's website (www.notificaram.es). By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Darunavir Aurovitas

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the blister pack, carton, or bottle after EXP. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Do not use this medication if you notice any change in the appearance of the tablets.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need in the pharmacy's SIGRE collection point. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Darunavir Aurovitas

• The active ingredient is darunavir (as propylene glycolate). Each film-coated tablet contains 800 mg of darunavir (as propylene glycolate).
• The other ingredients are:

Core of the tablet:microcrystalline cellulose (Grade 101), hydroxypropylcellulose, crospovidone (Type B), colloidal anhydrous silica, and magnesium stearate.

Tablet coating:Ready-to-use coating material (brown color): polyvinyl alcohol, macrogol 3350, red iron oxide (E172), titanium dioxide (E171), and talc.

Appearance of the product and package contents

Film-coated tablets of dark red color, oval, biconvex, with the mark "D" on one face and "800" on the other.

Darunavir Aurovitas film-coated tablets are available in blister packs and high-density polyethylene (HDPE) bottles with child-resistant polypropylene caps.

Package sizes:

Blister pack:30, 50, 60, 90, 100, and 120 film-coated tablets.

HDPE bottles:30 and 90 (3×30) film-coated tablets.

Not all package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Manufacturer:

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Or

Generis Farmacêutica, S.A.

Rua João de Deus, 19

2700-487 Amadora

Portugal

Or

Arrow Génériques

26 Avenue Tony Garnier

69007 Lyon

France

This medication is authorized in the member states of the European Economic Area with the following names:

Germany: Darunavir PUREN 800 mg film-coated tablets

Spain: Darunavir Aurovitas 800 mg film-coated tablets EFG

France: Darunavir Arrow 800 mg film-coated tablets

Netherlands: Darunavir Aurobindo 800 mg film-coated tablets

Poland: Darunavir Aurovitas

Portugal: Darunavir Generis

Date of the last revision of this leaflet: September 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/).