DARUNAVIR TILLOMED 400 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Darunavir Tillomed 400 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 Tillomed and what is it used for
2. What you need to know before you take Darunavir Tillomed
3. How to take Darunavir Tillomed
4. Possible side effects
5. Storage of Darunavir Tillomed
6. Contents of the pack and other information

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

What is Darunavir Tillomed?

Darunavir Tillomed 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. Darunavir reduces the amount of HIV in your body. This will improve your immune system and reduce the risk of diseases associated with HIV infection.

What is it used for?

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

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

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

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

Do not take Darunavir Tillomed:

• if you are allergicto 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 all the medicines you are taking, including those you bought without a prescription, herbal remedies, and those you have been given for other health problems.

Do not take 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 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 darunavir.

Darunavir does not cure HIV infection. While you are taking this medicine, you may still develop infections or other illnesses associated with HIV. Keep in regular contact with your doctor.

People taking darunavir may develop skin rashes. These are usually mild and do not require treatment. However, in rare cases, skin rashes can be severe and potentially life-threatening. If you develop a skin rash or experience any of the following symptoms, please contact your doctor immediately: rash, fever, swollen lymph nodes, swelling of the face, eyelids, lips, or tongue, difficulty breathing or swallowing, or mouth sores or blisters.

Patient who take darunavir and raltegravir (for HIV infection), may present with rashes (usually mild or moderate) more frequently than patients who take either of these medicines separately.

Tell your doctor about your situation BEFORE and DURING treatment

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

• Tell your doctor if you have ever had liver disease, including hepatitis B or C. Your doctor will assess the severity of your liver disease before deciding if you can take darunavir.
• Tell your doctor if you have diabetes. Darunavir may increase blood sugar levels.
• Tell your doctor immediately if you notice any symptoms of infection(for example, enlarged lymph nodes, 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 infections that have been present without 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 the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness that starts in the hands and feet and moves up towards the trunk of the body, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Tell your doctor if you have hemophilia. Darunavir may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides(for example, used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to lack of blood supply to the bone). The risk of osteonecrosis is increased in patients with advanced HIV disease or who have been treated with corticosteroids. Symptoms of osteonecrosis include joint pain or stiffness, difficulty walking, and limited range of motion in the affected bone. If you notice any of these symptoms, please contact 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 darunavir.

Children and adolescents

Darunavir 400 mg tablets are not used in children under 3 years of age or weighing less than 40 kg.

Taking Darunavir Tillomed 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 darunavir. The list can be found in the section “Do not take Darunavir Tillomed with any of the following medicines:”

In most cases, darunavir can be taken with HIV medicines from 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 carefully follow their instructions on which medicines can be combined.

The effects of darunavir may be reduced if you take any of the following products. 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. 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 treatment to lower cholesterol is most suitable for you based on your personal circumstances.
• Clarithromycin(antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus(for the treatment of 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 disorders. 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 medical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.
• Buprenorphine/naloxone(medicines for the treatment of opioid dependence).
• Salmeterol(medicine for the treatment of asthma).
• Artemether/lumefantrine(a combination of medicines to treat malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine(for the treatment of cancer).
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir, simeprevir(for the treatment of hepatitis C infection).
• Fentanyl, oxycodone, tramadol(for pain relief).
• Fesoterodine, solifenacin(for the treatment of urological disorders).

Your doctor may want to do some additional blood tests and in certain cases, it may be necessary to adjust the dose of some medicines because when combined, the therapeutic or adverse effects of these or darunavir may be affected. 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 high blood pressure in the pulmonary circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone(for depression and anxiety).
• Maraviroc(for HIV infection).
• Methadone(for narcotic dependence).
• 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 high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when given by injection, zolpidem(sedatives).
• Perphenazine, risperidone, thioridazine(for psychiatric conditions).
• Metformin(for type 2 diabetes).

This is nota complete list of medicines. Tell your doctor about allthe medicines you are taking.

Taking Darunavir Tillomed with food and drink

See section 3 “How to take Darunavir Tillomed.”

Pregnancy and breastfeeding

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

Due to the potential side effects in infants, women must not breastfeed if they are taking Darunavir Tillomed.

It is recommended that HIV-infected women do not breastfeed their babies to avoid transmitting the virus to them. If you are breastfeeding or thinking of breastfeeding, please consult your doctor.

Driving and using machines

Do not drive or use machines if you feel dizzy after taking Darunavir Tillomed.

Darunavir Tillomed 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 Tillomed

Follow the administration instructions of the medicine 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 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 400-milligram darunavir tablets are used only to obtain the 800-milligram dosage once a day.

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 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 food 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 two 400-milligram tablets 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 (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) with 150 milligrams of cobicistat or 100 milligrams of ritonavir once a day.

Or

• 600 milligrams of darunavir 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 with ritonavir, and from 12 years of age with cobicistat, with 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) with 100 milligrams of ritonavir or 150 mg of cobicistat once a day.

Dose for children from 3 years of age with ritonavir, and from 12 years of age with cobicistat, with 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) with 100 milligrams of ritonavir or 150 mg of cobicistat once a day.

Or

• 600 milligrams of darunavir 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 with ritonavir, and from 12 years of age with cobicistat, with 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 or 150 mg of cobicistat.
• 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 or cobicistat as your doctor recommends.

Child-resistant cap removal

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

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

If you take more Darunavir Tillomed than you should

Inform your doctor, pharmacist, or nurse immediately.

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

If you forget to take Darunavir Tillomed

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

If you vomit after taking Darunavir Tillomed with cobicistat or ritonavir

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

Contact your doctor if you are unsureof what to do if you miss a dose or if you vomit.

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

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

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

4. Possible side effects

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

Like all medications, this medication can cause side effects, although not all people experience them.

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

There have been reports of liver problems that can occasionally be severe. Your doctor will perform a blood test before starting darunavir. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood tests since 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, nausea, vomiting, loss of appetite, or pain, discomfort, or sensitivity 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. It is essential that you contact your doctor if you develop a rash. Your doctor will advise you on how to control the symptoms or if you should stop taking 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, dyspepsia, flatulence;
• headache, fatigue, dizziness, somnolence, numbness or pain in the hands or feet, loss of strength, difficulty staying asleep.

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

• chest pain, changes in the electrocardiogram, rapid heart rate;
• decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance;
• breathing difficulties, cough, nasal bleeding, throat irritation;
• stomach or mouth inflammation, heartburn, belching, dry mouth, abdominal discomfort, constipation, belching;
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night;
• hives, severe 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. In rare cases, these muscle disorders can be severe;
• reduced thyroid gland function. This can be seen in a blood test;
• hypertension, 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, somnolence, depression, anxiety, abnormal dreams, decreased libido.

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

• 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 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 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: an increase in some white blood cells.
• darunavir crystals in the kidney that cause kidney disease.

Some side effects are typical of HIV medications that belong to the same family as darunavir. These are:

• muscle pain, sensitivity, or weakness. In rare cases, these muscle disorders can be severe.

Reporting side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medications: https://www.notificarm.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Darunavir Tillomed

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the bottle after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be thrown down the drain or into the trash. Deposit the containers and medications you no longer need in the SIGRE Point of the pharmacy. If in 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

Darunavir Tillomed composition

• The active ingredient is darunavir. Each tablet contains 400 milligrams of darunavir.
• The other ingredients are:

Core of the tablet:silicified microcrystalline cellulose, crospovidone, hydroxypropylcellulose, sodium chloride, anhydrous colloidal silica, magnesium stearate, potassium polyacrylate.

Coating: Opadry II Beige 85F570070, which consists of partially hydrolyzed polyvinyl alcohol, macrogol 4000, titanium dioxide (E171), talc, yellow iron oxide (E172), red iron oxide (E172).

Appearance of the product and package contents

Beige film-coated tablet, oval, biconvex, engraved with "D" on one side and "400" on the other.

Darunavir Tillomed is available in: a white, opaque, high-density polyethylene (HDPE) plastic bottle containing 30 film-coated tablets, provided with a polypropylene (PP) cap with a child-resistant safety closure.

Package size:

Multiple package containing 60 film-coated tablets (2 packages of 30 tablets).

Marketing authorization holder and manufacturer

Marketing authorization holder

Laboratorios Tillomed Spain, S.L.U.

C/ Cardenal Marcelo Spínola 8, 1st floor, door F

28016 Madrid

Spain

Manufacturer

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

Ireland

Or

Tillomed Malta Limited

Malta Life Sciences Park

LS2.01.06 Industrial Estate

San Gwann, SGN 3000,

Malta

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

Germany Darunavir Tillomed 400 mg, film-coated tablets

Italy Darunavir Tillomed

Spain Darunavir Vivanta 400 mg film-coated tablets EFG

Date of the last revision of this prospectus:November 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/