Darunavir TilloMed: detailed information

PACKAGE LEAFLET

Package leaflet: Information for the user

Darunavir Tillomed 400 mg film-coated tablets

darunavir
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Darunavir Tillomed is and what it is used for
What you need to know before taking Darunavir Tillomed
How to take Darunavir Tillomed
Possible side effects
How to store Darunavir Tillomed
Contents of the pack and other information

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

What is Darunavir Tillomed?
Darunavir Tillomed contains the active substance darunavir. Darunavir Tillomed is an
antiretroviral medicine used to treat human immunodeficiency virus (HIV) infection. It
belongs to a group of medicines called protease inhibitors. Darunavir works by reducing
the amount of HIV in the body, improving the immune system, and reducing the risk of
developing HIV-related illnesses.

What is it used for?
Darunavir Tillomed 400 milligram tablets are used to treat adult patients and children (aged 3 years and older with a body weight of at least 40 kilograms) with HIV infection and:

who have not previously used other antiretroviral medicines, or
in certain patients who have previously used antiretroviral medicines (your doctor will determine for whom it should be prescribed).

Darunavir Tillomed must be taken in combination with a low dose of cobicistat or
ritonavir and other anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for your treatment.

2. What you need to know before taking Darunavir Tillomed

Do not take Darunavir Tillomed

if you are allergic to darunavir or to any of the other ingredients of this medicine (listed in section 6) or to cobicistat or ritonavir.
if you have severe liver problems. Consult 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 medicines taken orally,
inhaled, injected, or applied to the skin.
Do not take Darunavir Tillomed with any of the following medicines
If you are taking any of these medicines, ask your doctor how to switch to another
medicine.

Medicine	Purpose of the medicine
Avanafil	for the treatment of erectile dysfunction
Astemizole or terfenadine	for the treatment of allergic symptoms
Triazolam and oral midazolam (taken by mouth)	used to help sleep and/or reduce anxiety
Cisapride	for the treatment of certain stomach disorders
Colchicine (if you have kidney and/or liver problems)	for the treatment of gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	for the treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	for the treatment of migraine
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	for the treatment of certain heart problems, such as abnormal heart rhythm
Lovastatin, simvastatin and lomitapide	to lower cholesterol levels
Rifampicin	for the treatment of certain infections, such as tuberculosis
Lopinavir/ritonavir combination	this anti-HIV medicine belongs to the same class as darunavir
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	to treat prostate enlargement
Sildenafil	to treat 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	for the treatment of opioid-induced constipation
Dapoxetine	for the treatment of premature ejaculation
Domperidone	for the treatment of nausea and vomiting

Do not co-administer Darunavir Tillomed with products containing St. John’s Wort (Hypericum perforatum).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Darunavir Tillomed.
Darunavir is not a cure for HIV infection.
People taking darunavir may still develop infections or other illnesses associated with HIV infection. Regular follow-up with your doctor is necessary.
Patients taking darunavir may develop a rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
In patients taking darunavir and raltegravir (for HIV infection), skin rashes (generally mild or moderate) may occur more frequently than in patients taking each medicine separately.
Inform your doctor about your condition BEFORE and DURING treatment
Make sure to check the following points and inform your doctor if any of these apply to you.

Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe darunavir to you.
Inform your doctor if you have diabetes. Darunavir may increase 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 from prior infections may occur soon after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet spreading 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 (used, for example, to treat certain infections).
Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Some of the many risk factors for developing this disease may include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, pain, and aching (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
Darunavir has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor to evaluate whether you can take darunavir.
Children and adolescents
Darunavir Tillomed 400 milligram tablets must not be used in children under 3 years of age or weighing less than 40 kilograms.
Other medicines and Darunavir Tillomed
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are certain medicines that must not be co-administered with Darunavir Tillomed. These have been listed earlier in the section “Do not associate Darunavir Tillomed with any of the following medicines”.
In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir in combination with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dosage of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines you can take.
The effects of darunavir may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking Darunavir Tillomed, and your doctor may require 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 conditions), as the therapeutic effect or side effects of these medicines may be altered.
Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
Hormonal contraceptives containing estrogens or hormone replacement therapy. The effectiveness of darunavir may be reduced. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels due to drospirenone.
Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
Clarithromycin (antibiotic)
Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side 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 types of inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may be taken only after evaluation by your doctor and under close medical monitoring for corticosteroid-related side effects.
Buprenorphine/naloxone (medicines to treat opioid dependence)
Salmeterol (medicine to treat asthma)
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 or lung condition 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 require additional blood tests, and the dosage of other medicines may be adjusted because the therapeutic effect and side effects of these medicines or of Darunavir Tillomed may be affected when used together. Inform your doctor if you are taking:

Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
Alfentanil (a potent, short-acting injectable painkiller used during surgery)
Digoxin (to treat certain heart conditions)
Clarithromycin (antibiotic)
Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may be taken only after evaluation by your doctor.
Rifabutin (for bacterial infections)
Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the lung circulation)
Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
Maraviroc (to treat HIV infection)
Methadone (to treat opioid dependence)
Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
Colchicine (to treat gout or familial Mediterranean fever)
Bosentan (to treat high blood pressure in the lung circulation)
Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives)
Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)
Metformin (to treat type 2 diabetes)

This is not a complete list of medicines. Inform your doctor of all medicines you are taking.
Darunavir Tillomed with food and drink
See section 3 “How to take Darunavir Tillomed”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Women who are pregnant or breastfeeding should not take darunavir with ritonavir unless specifically instructed by their doctor. Women who are pregnant or breastfeeding should not take darunavir with cobicistat.
Due to the potential for adverse effects in infants, women must not breastfeed while receiving Darunavir Tillomed.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, talk to your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking darunavir.
Darunavir Tillomed contains sodium.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet and is therefore essentially “sodium-free”.

3. How to take Darunavir Tillomed

Use this medicine exactly as stated in this leaflet or as directed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Even if you feel better, do not stop taking Darunavir Tillomed with cobicistat or ritonavir without first talking to your doctor.
After starting treatment, do not change the dose, dosage form, or stop therapy without your doctor’s instructions.
The 400-milligram tablets of Darunavir Tillomed should only be used to construct the 800-milligram once-daily regimen.

Dosage for adults who have not previously taken antiretroviral medicines
(your doctor will assess this)
The usual dose of Darunavir Tillomed is 800 milligrams (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) once daily.
You must take Darunavir Tillomed every day, always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. Darunavir cannot work optimally without cobicistat or ritonavir and food. You must eat a meal or snack within 30 minutes before taking Darunavir Tillomed and cobicistat or ritonavir. The type of food consumed does not matter. Even if you feel better, do not stop taking Darunavir Tillomed and cobicistat or ritonavir before speaking with your doctor.

Instructions for adults

Take two 400-milligram tablets at the same time each day.
Take Darunavir Tillomed always with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
Take Darunavir Tillomed with food.
Swallow the tablets with a drink such as water or milk.
Take other HIV medicines used in combination with Darunavir Tillomed and cobicistat or ritonavir as directed by your doctor.

Dosage for adults who have previously taken antiretroviral medicines
(your doctor will assess this)
The dose is:

800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily. OR
600 milligrams of Darunavir Tillomed with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is most appropriate.

Dosage for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines
(your child’s doctor will determine this condition)

The usual dose of Darunavir Tillomed is 800 milligrams (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily.

Dosage for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have previously taken antiretroviral medicines
(your child’s doctor will determine this condition)
The dose is:

800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily. OR
600 milligrams of Darunavir Tillomed with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is most appropriate.

Instructions for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms

Take 800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) at the same time each day.
Take Darunavir Tillomed always with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
Take Darunavir Tillomed with food.
Swallow the tablets with a drink such as water or milk.
Take other HIV medicines used in combination with Darunavir Tillomed and ritonavir or cobicistat as directed by your doctor.

Removing the child-resistant cap
The plastic bottle has a child-resistant cap and must be opened as follows:

Press down on the plastic screw cap while turning it counterclockwise.
Remove the unscrewed cap.

If you take more Darunavir Tillomed than you should
Contact your doctor, pharmacist, or nurse immediately.

If you forget to take Darunavir Tillomed
If you remember within 12 hours, take the missed tablets immediately. Always take the tablets with cobicistat or ritonavir and with food. If you remember after 12 hours, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.

If you vomit after taking Darunavir Tillomed and cobicistat or ritonavir
If you vomit within 4 hours of taking the medicine, take another dose of Darunavir Tillomed and cobicistat or ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, you do not need to take another dose of Darunavir Tillomed and cobicistat or ritonavir until the next scheduled dose.
Contact your doctor if you are unsure about what to do if you miss a dose or vomit.

Do not stop treatment with Darunavir Tillomed without first discussing it with your doctor.
Anti-HIV medicines can make you feel better. Do not stop taking darunavir, even if you feel better. Talk to your doctor first.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV therapy, an increase in weight and in blood lipid and glucose levels may occur. This is partly related to the recovery of health status 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 side effects, although not everyone experiences them.
Tell your doctor if you develop any of the following side effects.

Liver problems have been reported, which occasionally may be serious. Your doctor will need to carry out blood tests before starting treatment with Darunavir Tillomed. If you have chronic hepatitis B or C, your doctor must monitor your blood tests more frequently, 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, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rashes (more frequent when used in combination with raltegravir), itching. These rashes are usually mild or moderate in severity. A rash may also be a symptom of a rare but serious condition. It is important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether Darunavir Tillomed should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

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

Diarrhea

Common side effects (may affect up to 1 in 10 people):

Vomiting, nausea, abdominal pain or bloating, indigestion, flatulence
Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of strength, difficulty falling asleep

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

Chest pain, changes in electrocardiogram, rapid heartbeat
Decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, balance disorders
Breathing difficulties, cough, nosebleeds, sore throat
Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
Hives, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
Muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
Slowed thyroid function. This can be detected through a blood test.
High blood pressure, flushing
Red eyes or dry eyes
Fever, leg swelling due to fluid retention, malaise, irritability, pain
Symptoms of infection, herpes simplex
Erectile dysfunction, breast enlargement
Sleep disturbances, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

A reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial or lymph node swelling, increased eosinophils (a type of white blood cell), effects on liver, kidneys or lungs]
Heart attack, slowed heartbeat, palpitations
Visual disturbances
Chills, feeling unwell
A feeling of confusion or disorientation, altered mood, restlessness
Fainting, epileptic seizures, change or loss of taste
Mouth ulcers, blood in vomit, inflammation of the lips, dry lips, coated tongue
Runny nose
Skin lesions, dry skin
Stiffness of muscles or joints, joint pain with or without inflammation
Changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells.
Deposition of darunavir crystals in the kidney, leading to kidney disease.

Some side effects are typical of anti-HIV medicines in the same class as Darunavir Tillomed. These are:

Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Darunavir Tillomed

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle after "EXP.". The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Pack contents and other information

What Darunavir Tillomed contains

The active substance is darunavir. Each tablet contains 400 mg of darunavir.
The other ingredients are:
Tablet core: silicified microcrystalline cellulose, crospovidone, hydroxypropylcellulose, sodium chloride, anhydrous colloidal silica, magnesium stearate, potassium polyacrylate.

Coating: Opadry II beige 85F570070 composed of partially hydrolysed polyvinyl alcohol, macrogol 4000, titanium dioxide (E171), talc, yellow iron oxide (E172), red iron oxide (E172).

Description of the appearance of Darunavir Tillomed and pack contents

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

Darunavir Tillomed tablets are available in: opaque white high-density polyethylene (HDPE) bottle containing 30 tablets, fitted with a child-resistant polypropylene (PP) closure.

Pack sizes: multiple packs containing 60 (2 packs of 30) film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale Richard 1, Tower A
20143, Milan
Italy

Manufacturer
Tillomed Malta Limited,
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the following European Economic Area Member States under the following names:
Germany Darunavir Tillomed 400 mg, Filmtabletten
Italy Darunavir Tillomed
Spain Darunavir Tillomed 400 mg, comprimidos recubiertos con película EFG

PACKAGE LEAFLET

Patient Information Leaflet: Information for the User

Darunavir Tillomed 600 mg film-coated tablets

darunavir
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Darunavir Tillomed is and what it is used for
What you need to know before taking Darunavir Tillomed
How to take Darunavir Tillomed
Possible side effects
How to store Darunavir Tillomed
Contents of the pack and other information

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

What it is used for
Darunavir Tillomed is used to treat adult patients and children aged 3 years and older weighing
at least 15 kilograms who have HIV infection and who have previously used other
antiretroviral medicines.
Darunavir Tillomed must be taken in combination with a low dose of ritonavir and other
anti-HIV medicines. Your doctor will discuss with you the most appropriate combination of
medicines for your treatment.

2. What you need to know before taking Darunavir Tillomed

Do not take Darunavir Tillomed

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 for advice 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 medicines taken orally, inhaled, injected, or applied to the skin.
Do not take Darunavir Tillomed with any of the following medicines:
If you are currently taking any of these medicines, ask your doctor how to switch to another medicine.

Medicine	Purpose of the medicine
Avanafil	for the treatment of erectile dysfunction
Astemizole or terfenadine	for the treatment of allergic symptoms
Triazolam and oral midazolam (taken by mouth)	used to promote sleep and/or reduce anxiety
Cisapride	for the treatment of certain stomach disorders
Colchicine (if you have kidney and/or liver problems)	for the treatment of gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	for the treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	for the treatment of migraine
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	for the treatment of certain heart problems, such as irregular heartbeat
Loxapine, simvastatin and lomitapide	to lower cholesterol levels
Rifampicin	for the treatment of certain infections, such as tuberculosis
Combination of lopinavir/ritonavir	this anti-HIV medicine belongs to the same class as darunavir
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	to treat prostate enlargement
Sildenafil	to treat 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	for the treatment of opioid-induced constipation
Dapoxetine	for the treatment of premature ejaculation
Domperidone	for the treatment of nausea and vomiting

Do not co-administer Darunavir Tillomed with products containing St John’s wort (Hypericum perforatum).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Darunavir Tillomed.
Darunavir is not a cure for HIV infection.
People taking darunavir may still develop infections or other illnesses associated with HIV infection. Regular follow-up with your doctor is necessary.
Patients taking darunavir may develop a rash. Rarely, the rash can become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
Skin rashes (generally mild or moderate) may occur more frequently in patients taking darunavir and raltegravir (for HIV infection) than in patients taking each medicine separately.
Inform your doctor about your condition BEFORE and DURING treatment
Please check the following points and inform your doctor if any of these apply to you.

Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe darunavir to you.
Inform your doctor if you have diabetes. Darunavir may increase 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 from prior infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, allowing the body to fight infections that may have been present without causing obvious symptoms.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing 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 (used, for example, to treat certain infections).
Inform your doctor if you notice any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Some of the many risk factors for developing this disease may include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, pain, and aching (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
Darunavir has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor to evaluate whether you can take darunavir.
Children
Darunavir Tillomed must not be used in children under 3 years of age or weighing less than 15 kilograms.
Other medicines and Darunavir Tillomed
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are certain medicines that must not be co-administered with Darunavir Tillomed. These have been listed earlier in the section “Do not co-administer Darunavir Tillomed with any of the following medicines”.
In most cases, darunavir can be co-administered with anti-HIV medicines belonging to another class [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir in combination with ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dosage of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines you may take.
The effects of darunavir may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking Darunavir Tillomed, and your doctor may require 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 conditions), as the therapeutic effect or side effects of these medicines may be altered.
Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
Hormonal contraceptives containing oestrogens or hormone replacement therapy. The effectiveness of darunavir may be reduced. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels caused by drospirenone.
Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
Clarithromycin (an antibiotic)
Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side 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 muscular conditions, and other types of inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under close monitoring for corticosteroid-related side effects.
Buprenorphine/naloxone (medicines to treat opioid dependence)
Salmeterol (medicine for the treatment of asthma)
Artemether/lumefantrine (a combination of medicines for the treatment of malaria)
Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)
Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension)
Glecaprevir/pibrentasvir (to treat hepatitis C infection)
Fentanyl, oxycodone, tramadol (for pain treatment)
Fesoterodine, solifenacin (for the treatment of urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted because the therapeutic effect and side effects of these medicines or of Darunavir Tillomed may be affected when co-administered. Inform your doctor if you are taking:

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

This is not a complete list of medicines. Inform your doctor of all medicines you are taking.
Darunavir Tillomed with food and drink
See section 3 “How to take Darunavir Tillomed”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, planning a pregnancy, or breastfeeding. Women who are pregnant or breastfeeding should not take darunavir with ritonavir unless specifically instructed by their doctor. Women who are pregnant or breastfeeding should not take darunavir with cobicistat.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving Darunavir Tillomed.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking darunavir.
Darunavir Tillomed contains sodium.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet and is therefore essentially “sodium-free”.

3. How to take Darunavir Tillomed

Take this medicine exactly as described in this leaflet or as directed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Even if you feel better, do not stop taking Darunavir Tillomed and ritonavir before speaking with your doctor.
After starting treatment, do not change the dose, dosage form, or stop treatment without instructions from your doctor.

Dose for adults who have not previously taken antiretroviral medicines (your doctor will assess this)
Different doses of darunavir may be required, which cannot be administered using these 600 milligram tablets. Other dosage strengths of Darunavir Tillomed are available.

Dose for adults who have previously taken antiretroviral medicines (your doctor will assess this)
The dose is:

600 milligrams of Darunavir Tillomed with 100 milligrams of ritonavir twice daily. OR
800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) with 100 milligrams of ritonavir once daily. The 400 milligram and 800 milligram tablets of Darunavir Tillomed must only be used to construct the 800 milligram once-daily regimen.

Discuss with your doctor which dose is most appropriate.

Instructions for adults

Always take Darunavir Tillomed with ritonavir. Darunavir cannot work optimally without ritonavir.
In the morning, take one 600 milligram tablet of Darunavir Tillomed with 100 milligrams of ritonavir.
In the evening, take one 600 milligram tablet of Darunavir Tillomed with 100 milligrams of ritonavir.
Take Darunavir Tillomed with food. Darunavir cannot act effectively without food. The type of food consumed does not matter.
Swallow the tablets with a drink such as water or milk.

Dose for children aged 3 years and older and weighing at least 15 kilograms who have not previously taken antiretroviral medicines (your doctor will determine this condition)
Your 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 of 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.

Weight	One dose of darunavir is	One 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
Dose for children aged 3 years and older and weighing at least
15 kilograms who have previously taken antiretroviral medicines (this condition will be
determined by the doctor)
The doctor will calculate the correct dose based on the child's body weight (see table below). The doctor will decide whether it is appropriate for the child to take the once-daily or twice-daily dose. 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. Other dosage strength tablets are available to build the appropriate dosing regimen.
Dose twice daily

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
More than 40 kilograms*	600 milligrams of darunavir + 100 milligrams of ritonavir twice daily

For children aged 12 years and older and weighing at least 40 kilograms, the child's doctor will determine whether darunavir 800 milligrams once daily can be used. This cannot be administered with these 600-milligram tablets.
Other darunavir dosage strengths are available.
Once-daily dosing

Weight	One dose of darunavir is	One 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
Instructions for children

The child must take Darunavir Tillomed always together with ritonavir. Darunavir cannot work optimally without ritonavir.
The child must take the appropriate doses of Darunavir Tillomed and ritonavir twice daily or once daily. If Darunavir Tillomed is prescribed twice daily, the child must take one dose in the morning and one dose in the evening. The doctor will determine which regimen is most appropriate for the child.
The child must take Darunavir Tillomed with food. Darunavir cannot work effectively without food. The type of food taken does not matter.
The child must swallow the tablets with a drink such as water or milk.

Removing the child-resistant cap
The plastic bottle has a child-resistant cap and must be opened as follows:

Push down on the plastic screw cap while turning it counterclockwise.
Remove the unscrewed cap.

If you take more Darunavir Tillomed than you should
Contact a doctor, pharmacist, or nurse immediately.
If you forget to take Darunavir Tillomed
If you realize within 6 hours, take the tablets immediately. Always take the tablets together with ritonavir and food. If you realize after 6 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for the forgotten dose.
If vomiting occurs after taking Darunavir Tillomed and ritonavir
If vomiting occurs within 4 hours of taking the medicine, take another dose of Darunavir Tillomed and ritonavir with 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 Tillomed 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 treatment with Darunavir Tillomed without first discussing it with your doctor.
Anti-HIV medicines can make you feel better. Do not stop taking darunavir, even if you feel better. Talk to your doctor first.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor if you develop any of the following side effects.

Liver problems have been reported, which occasionally can be serious. Your doctor will carry out blood tests before starting treatment with Darunavir Tillomed. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, 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, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. These rashes are usually mild or moderate. A rash may also be a symptom of a rare, serious condition. It is therefore important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether Darunavir Tillomed should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

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

Diarrhea

Common side effects (may affect up to 1 in 10 people):

Vomiting, nausea, abdominal pain or bloating, indigestion, flatulence
Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of strength, difficulty falling asleep

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

Chest pain, changes in electrocardiogram, rapid heartbeat
Decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, balance disorders
Breathing difficulties, cough, nosebleeds, sore throat
Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
Hives, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
Muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
Slowed thyroid function. This can be detected through a blood test.
High blood pressure, flushing
Red eyes or dry eyes
Fever, leg swelling due to fluid accumulation, malaise, irritability, pain
Symptoms of infection, herpes simplex
Erectile dysfunction, breast enlargement
Sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

A reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial or lymph node swelling, increased eosinophils (a type of white blood cell), effects on liver, kidneys, or lungs]
Heart attack, slow heartbeat, palpitations
Visual disturbances
Chills, feeling unwell
A sensation of confusion or disorientation, altered mood, restlessness
Fainting, epileptic seizures, change or loss of taste
Mouth ulcers, blood in vomit, inflammation of the lips, dry lips, coated tongue
Runny nose
Skin lesions, dry skin
Stiffness of muscles or joints, joint pain with or without inflammation
Changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
Deposition of darunavir crystals in the kidney leading to kidney disease

Some side effects are typical of anti-HIV medicines belonging to the same class as Darunavir Tillomed. These are:

Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Darunavir Tillomed

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle after "EXP.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Darunavir Tillomed contains

The active substance is darunavir. Each tablet contains 600 mg of darunavir.
The other excipients are: Tablet core: silicified microcrystalline cellulose, crospovidone, hydroxypropylcellulose, sodium chloride, anhydrous colloidal silica, magnesium stearate, potassium polyacrylate. Coating: Opadry II beige 85F570070 composed of partially hydrolysed polyvinyl alcohol, macrogol 4000, titanium dioxide (E171), talc, yellow iron oxide (E172), red iron oxide (E172).

Description of the appearance of Darunavir Tillomed and contents of the pack
Beige, oval, biconvex, film-coated tablets, marked with "D" on one side and "600" on the other.
Darunavir Tillomed tablets are available in: opaque high-density polyethylene (HDPE) bottles, white in colour, containing 30 tablets, with a child-resistant closure made of polypropylene (PP).
Pack sizes: multi-packs containing 60 tablets (2 packs of 30) film-coated tablets. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale Richard 1, Tower A
20143, Milan
Italy

Manufacturer
Tillomed Malta Limited,
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the European Economic Area countries
under the following names:
Germany Darunavir Tillomed 600 mg, Filmtabletten
Italy Darunavir Tillomed
Spain Darunavir Tillomed 600 mg, comprimidos recubiertos con película EFG

PACKAGE LEAFLET

Package leaflet: information for the user

Darunavir Tillomed 800 mg film-coated tablets

darunavir
Generic medicine
Please read this entire leaflet carefully before taking this medicine, as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Darunavir Tillomed is and what it is used for
What you need to know before taking Darunavir Tillomed
How to take Darunavir Tillomed
Possible side effects
How to store Darunavir Tillomed
Contents of the pack and other information

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

What Darunavir Tillomed is
Darunavir Tillomed contains the active substance darunavir. Darunavir Tillomed is an
antiretroviral medicine used to treat human immunodeficiency virus (HIV) infection. It
belongs to a group of medicines called protease inhibitors. Darunavir works by reducing the
amount of HIV in the body, improving the immune system, and reducing the risk of HIV-related
diseases.
What it is used for
Darunavir Tillomed 800 milligram tablets are used to treat adult patients and children (aged 3 years and older with a body weight of at least 40 kilograms) with HIV infection and

who have not previously used other antiretroviral medicines, or
in certain patients who have previously used antiretroviral medicines (your doctor will determine whether it is appropriate for you).

2. What you need to know before taking Darunavir Tillomed

Do not take Darunavir Tillomed

if you are allergic to darunavir or to any of the other ingredients of this medicine (listed in section 6) or to cobicistat or ritonavir.
if you have severe liver problems. Consult your doctor if you are unsure about the severity of your liver disease. You may need further tests.

Inform your doctor about all the medicines you are taking, including medicines taken orally,
inhaled, injected, or applied to the skin.
Do not take Darunavir Tillomed with any of the following medicines.
If you are currently taking one of these medicines, ask your doctor how to switch to another
medicine.

Medicine	Purpose of the medicine
Avanafil	for the treatment of erectile dysfunction
Astemizole or terfenadine	for the treatment of allergic symptoms
Triazolam and oral midazolam (taken by mouth)	used to help sleep and/or reduce anxiety
Cisapride	for the treatment of certain stomach disorders
Colchicine (if you have kidney and/or liver problems)	for the treatment of gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	for the treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	for the treatment of migraine
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	for the treatment of certain heart problems, such as irregular heartbeats
Lovastatin, simvastatin and lomitapide	to lower cholesterol levels
Rifampicin	for the treatment of certain infections, such as tuberculosis
Combination of lopinavir/ritonavir	this anti-HIV medicine belongs to the same class as darunavir
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	to treat benign prostatic hyperplasia
Sildenafil	to treat 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	for the treatment of opioid-induced constipation
Dapoxetine	for the treatment of premature ejaculation
Domperidone	for the treatment of nausea and vomiting

Do not co-administer Darunavir Tillomed with products containing St. John's Wort (Hypericum perforatum).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Darunavir Tillomed.
Darunavir is not a cure for HIV infection.
People taking darunavir may still develop infections or other illnesses associated with HIV infection. Regular follow-up with your doctor is necessary.
Patients taking darunavir may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a rash.
Skin rashes (generally mild or moderate) may occur more frequently in patients taking darunavir and raltegravir (for HIV infection) than in patients taking each medicine separately.
Inform your doctor about your condition BEFORE and DURING treatment
Make sure to check the following points and inform your doctor if any of them apply to you.

Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe darunavir to you.
Inform your doctor if you have diabetes. Darunavir may increase 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 from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing 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 (used, for example, to treat certain infections).
Inform your doctor if you notice any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Some of the many risk factors for developing this condition may include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, aches, and sharp pains (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
Darunavir has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor to evaluate whether you can take darunavir.
Children and adolescents
Darunavir Tillomed 800 milligram tablets must not be used in children under 3 years of age or with body weight below 40 kilograms.
Other medicines and Darunavir Tillomed
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are some medicines that must not be co-administered with Darunavir Tillomed. These have been listed earlier in the section “Do not associate Darunavir Tillomed with any of the following medicines”.
In most cases, darunavir can be co-administered with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir co-administered with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dosage of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines you may take.
The effects of darunavir may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking Darunavir Tillomed, and your doctor may require 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 conditions), as the therapeutic effect or side effects of these medicines may be altered.
Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
Hormonal contraceptives containing estrogens or hormone replacement therapy. The effectiveness of darunavir may be reduced. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels caused by drospirenone.
Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
Clarithromycin (antibiotic)
Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side 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 muscular conditions, and other types of inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under close monitoring for corticosteroid-related side effects.
Buprenorphine/naloxone (medicines to treat opioid dependence)
Salmeterol (medicine to treat asthma)
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 or lung condition called pulmonary arterial hypertension)
Glecaprevir/pibrentasvir (to treat hepatitis C infection)
Fentanyl, oxycodone, tramadol (to treat pain)
Fesoterodine, solifenacin (to treat urological disorders).

Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
Alfentanil (a potent, short-acting injectable painkiller used during surgery)
Digoxin (to treat certain heart conditions)
Clarithromycin (antibiotic)
Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may be taken only after evaluation by your doctor.
Rifabutin (for bacterial infections)
Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for high blood pressure in the lung circulation)
Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
Maraviroc (to treat HIV infection)
Methadone (to treat opioid dependence)
Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
Colchicine (to treat gout or familial Mediterranean fever)
Bosentan (to treat high blood pressure in the lung circulation)
Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives)
Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)
Metformin (to treat type 2 diabetes)

This is not a complete list of medicines. Inform your doctor of all medicines you are taking.
Darunavir Tillomed with food and drink
See section 3 “How to take Darunavir Tillomed”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, planning a pregnancy, or breastfeeding. Women who are pregnant or breastfeeding should not take darunavir with ritonavir unless specifically instructed by their doctor. Women who are pregnant or breastfeeding should not take darunavir with cobicistat.
Due to the possibility of adverse effects in infants, women must not breastfeed while receiving Darunavir Tillomed.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking darunavir.
Darunavir Tillomed contains sodium.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, thus essentially “sodium-free”.

3. How to take Darunavir Tillomed

Use this medicine exactly as stated in this leaflet or as instructed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Even if you feel better, do not stop taking Darunavir Tillomed and cobicistat or ritonavir without first talking to your doctor.
After starting treatment, do not change the dose, dosage form, or stop treatment without your doctor’s instructions.
The 800 milligram tablets of Darunavir Tillomed are intended only for daily use.

Dose for adults who have not previously taken antiretroviral medicines (your doctor will assess this)
The usual dose of Darunavir Tillomed is 800 milligrams (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) once daily.
You must take Darunavir Tillomed every day, always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir, and with food. Darunavir cannot work optimally without cobicistat or ritonavir and without food. You must eat a meal or snack within 30 minutes before taking Darunavir Tillomed and cobicistat or ritonavir. The type of food is not important. Even if you feel better, do not stop taking Darunavir Tillomed and cobicistat or ritonavir before speaking with your doctor.

Instructions for adults

Take one 800 milligram tablet at the same time each day.
Take Darunavir Tillomed always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
Take Darunavir Tillomed with food.
Swallow the tablets with a drink such as water or milk.
Take the other HIV medicines used in combination with Darunavir Tillomed and cobicistat or ritonavir as instructed by your doctor.

Dose for adults who have previously taken antiretroviral medicines (your doctor will assess this)
The dose is:

800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily. OR
600 milligrams of Darunavir Tillomed with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is most appropriate.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (your child’s doctor will determine this)

The usual dose of Darunavir Tillomed is 800 milligrams (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (your child’s doctor will determine this)
The dose is:

800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily. OR
600 milligrams of Darunavir Tillomed with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is most appropriate.

Instructions for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms

Take 800 milligrams of Darunavir Tillomed (2 tablets containing 400 milligrams of Darunavir Tillomed or 1 tablet containing 800 milligrams of Darunavir Tillomed) at the same time each day.
Take Darunavir Tillomed always together with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
Take Darunavir Tillomed with food.
Swallow the tablets with a drink such as water or milk.
Take the other HIV medicines used in combination with Darunavir Tillomed and ritonavir or cobicistat as instructed by your doctor.

Opening the child-resistant cap
The plastic bottle has a child-resistant cap and must be opened as follows:

Press down on the plastic screw cap while turning it counterclockwise.
Remove the unscrewed cap.

If you take more Darunavir Tillomed than you should
Contact a doctor, pharmacist, or nurse immediately.

If you forget to take Darunavir Tillomed
If you remember within 12 hours, take the missed tablets immediately. Always take the tablets together with cobicistat or ritonavir and with food. If you remember after 12 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for the forgotten dose.

If you vomit after taking Darunavir Tillomed and cobicistat or ritonavir
If you vomit within 4 hours of taking the medicine, take another dose of Darunavir Tillomed and cobicistat or ritonavir with 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 Tillomed and cobicistat or 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 treatment with Darunavir Tillomed without first discussing it with your doctor.
Anti-HIV medicines can make you feel better. Do not stop taking darunavir, even if you feel better. Speak to your doctor first.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV therapy, an increase in weight and in blood levels of lipids and glucose may occur. This is partly related to the recovery of health status 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 side effects, although not everybody gets them.

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

Liver problems have been reported, which occasionally can be serious. Your doctor will need to perform blood tests before starting treatment with Darunavir Tillomed. If you have chronic hepatitis B or C, your doctor must monitor your blood tests more frequently, 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, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

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

Diarrhea

Common side effects (may affect up to 1 in 10 people):

Vomiting, nausea, abdominal pain or bloating, indigestion, flatulence
Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of strength, difficulty falling asleep

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

Chest pain, changes in electrocardiogram, rapid heartbeat
Decreased or abnormal skin sensation, tingling sensation, attention disorders, memory loss, balance disorders
Breathing difficulties, cough, nosebleeds, throat irritation
Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
Hives, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
Muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
Slowed thyroid function. This can be detected through a blood test.
High blood pressure, flushing
Red eyes or dry eyes
Fever, swelling of legs due to fluid accumulation, malaise, irritability, pain
Symptoms of infection, herpes simplex
Erectile dysfunction, breast enlargement
Sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

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 in the blood), effects on liver, kidneys or lungs]
Heart attack, slow heartbeat, palpitations
Visual disturbances
Chills, feeling unwell
A sensation of confusion or disorientation, altered mood, restlessness
Fainting, seizures, change or loss of taste
Mouth ulcers, blood in vomit, inflammation of the lips, dry lips, coated tongue
Runny nose
Skin lesions, dry skin
Stiffness of muscles or joints, joint pain with or without inflammation
Changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
Deposition of darunavir crystals in the kidney, leading to kidney disease

Some side effects are typical of anti-HIV medicines belonging to the same class as Darunavir Tillomed. These are:

Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Darunavir Tillomed

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle after "EXP.". The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Darunavir Tillomed contains

The active substance is darunavir. Each tablet contains 800 mg of darunavir.
The other ingredients are: Tablet core: silicified microcrystalline cellulose, crospovidone, hydroxypropylcellulose, sodium chloride, anhydrous colloidal silica, magnesium stearate, potassium polyacrylate. Coating: Opadry II brown 85F565137 composed of partially hydrolysed polyvinyl alcohol, macrogol 4000, titanium dioxide (E171), talc, red iron oxide (E172).

Description of the appearance of Darunavir Tillomed and package contents
Brown, oval, biconvex, film-coated tablets, marked with “D” on one side and “800” on the other.
Darunavir Tillomed tablets are available in: opaque high-density polyethylene (HDPE) bottles, white in colour, containing 30 tablets, fitted with a child-resistant closure made of polypropylene (PP).
Pack sizes: 30 film-coated tablets or multiple packs containing 90 tablets (3 packs of 30) film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Tillomed Italia S.r.l.
Viale Richard 1, Tower A, 20143, Milan, Italy
Manufacturer
Tillomed Malta Limited,
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Germany Darunavir Tillomed 800 mg, Filmtabletten
Italy Darunavir Tillomed
Spain Darunavir Tillomed 800 mg, comprimidos recubiertos con película EFG