Darunavir Aurovitas

Leaflet accompanying the packaging: patient information

Darunavir Aurovitas, 600 mg, film-coated tablets

Darunavir

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Darunavir Aurovitas and what is it used for
• 2. Important information before taking Darunavir Aurovitas
• 3. How to take Darunavir Aurovitas
• 4. Possible side effects
• 5. How to store Darunavir Aurovitas
• 6. Contents of the packaging and other information

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

What is Darunavir Aurovitas

Darunavir Aurovitas contains the active substance darunavir. Darunavir Aurovitas is an antiretroviral medicine used to treat HIV infection. It belongs to a group of protease inhibitors. The action of Darunavir Aurovitas is to reduce the amount of HIV virus in the body. This helps the immune system and reduces the risk of developing diseases related to HIV infection.

What is it used for

Darunavir Aurovitas is used to treat adults and children (from 3 years of age and weighing at least 15 kg) infected with HIV, including those who have previously been treated with other antiretroviral medicines. Darunavir Aurovitas should be taken in combination with a low dose of ritonavir and other HIV medicines. The best combination of medicines for the patient is determined by the doctor.

2. Important information before taking Darunavir Aurovitas

When not to take Darunavir Aurovitas

• if the patient is allergicto darunavir or any of the other ingredients of this medicine (listed in section 6) or to ritonavir;
• if the patient has severe liver problems. In case of doubts about liver problems and their nature, the patient should consult a doctor. It may be necessary to perform some additional tests.

The patient should tell their doctor about allmedicines they are taking, including those taken orally, inhaled, injected, or applied to the skin.

Do not take Darunavir Aurovitas with the following medicines

If the patient is taking any of the following medicines, they should consult their doctor about changing their treatment.

During treatment with Darunavir Aurovitas, the patient must not take preparations containing St. John's Wort (Hypericum perforatum).

Warnings and precautions

Before starting treatment with Darunavir Aurovitas, the patient should discuss it with their doctor, pharmacist, or nurse. Darunavir Aurovitas is not a cure for HIV infection. Patients taking Darunavir Aurovitas are still at risk of developing infections or other diseases related to the presence of HIV, so they should maintain regular contact with their doctor. In patients taking Darunavir Aurovitas, a skin rash may occur. Rarely, it can be severe or life-threatening. If a rash occurs, the patient should contact their doctor. A rash (usually mild or moderate) may occur more frequently in patients taking Darunavir Aurovitas and raltegravir than in patients taking either medicine separately.

When to inform the doctor about health status BEFORE and DURING treatment

After reading the following points, the patient should inform their doctor if any of them apply to them.

• The patient should inform their doctor if they have had liver disease in the past, including viral hepatitis B or C. The doctor will assess how severe the disease was before deciding whether it is possible to take Darunavir Aurovitas.
• The patient should inform their doctor if they have diabetes. Darunavir Aurovitas may increase blood sugar levels.
• The patient should immediately inform their doctor if they notice signs of infection (e.g., swollen lymph nodes, fever). In some patients with advanced HIV infection and a history of opportunistic infections, subjective and objective symptoms of inflammation related to previous infections may appear immediately after starting antiretroviral therapy. It is believed that the appearance of such symptoms is related to the strengthening of the body's immune response, which allows the body to fight existing asymptomatic infections.
• In addition to opportunistic infections, autoimmune diseases (diseases that occur when the immune system attacks healthy tissues) may also occur after starting antiretroviral therapy. Autoimmune diseases can occur many months after starting treatment. If the patient notices signs of infection or other symptoms, such as muscle weakness, weakness starting from the hands and feet and progressing towards the torso, palpitations, tremors, or hyperactivity, they should contact their doctor as soon as possible to start necessary treatment.
• The patient should inform their doctor if they have hemophilia. Darunavir Aurovitas may increase the risk of bleeding.
• The patient should inform their doctor about an allergy to sulfonamides (e.g., used to treat certain infections).
• The patient should inform their doctor about musculoskeletal disorders. In some patients taking combination antiretroviral therapy, a bone disease called osteonecrosis (bone death due to insufficient blood supply) may develop. Risk factors for developing this disease include: duration of combination antiretroviral therapy, use of corticosteroids, alcohol consumption, state of deep immunosuppression, increased body mass index, and others. Symptoms of osteonecrosis include: pain and stiffness of the joints (especially hips, knees, or shoulders) and difficulty moving. The patient should inform their doctor if they experience any of these symptoms.

Elderly patients

Darunavir Aurovitas has been used in only a small number of patients aged 65 and over. If the patient belongs to this age group, they should consult their doctor about whether they can take Darunavir Aurovitas.

Children and adolescents

Darunavir Aurovitas should not be used in children under 3 years of age or weighing less than 15 kg.

Darunavir Aurovitas and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. Some medicines must not be takenwith Darunavir Aurovitas. A list of these substances can be found in the section "Do not take Darunavir Aurovitas with the following medicines". In most cases, Darunavir Aurovitas can be taken with HIV medicines from another group [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and fusion inhibitors]. However, studies have not been conducted on the simultaneous use of Darunavir Aurovitas and ritonavir with all PIs (protease inhibitors), and it should not be used in combination with other protease inhibitors. In some cases, it may be necessary to change the dosage of other medicines. Therefore, in each case, the patient should inform their doctor about the use of other HIV medicines and strictly follow the doctor's recommendations regarding the simultaneous use of other medicines. The effectiveness of Darunavir Aurovitas may be reduced when taken with one of the following products. The patient should inform their doctor about taking:

• phenobarbital, phenytoin (antiepileptic drugs);
• dexamethasone (corticosteroid);
• efavirenz (used to treat HIV infection);
• rifapentine, rifabutin (medicines used to treat certain infections, such as tuberculosis);
• saquinavir (used to treat HIV infection).

Taking Darunavir Aurovitas may affect the effectiveness of other medicines, and the doctor may order additional blood tests. The patient should inform their doctor about taking:

• amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (medicines used to treat heart diseases) due to the possibility of increased therapeutic and adverse effects of these medicines;
• apixaban, edoxaban dabigatran, rivaroxaban, warfarin, clopidogrel (anticoagulant medicines) due to the possibility of increased therapeutic and adverse effects of these medicines;
• hormonal contraceptives and hormone replacement therapy containing estrogens. Darunavir Aurovitas may reduce their effectiveness; when used to prevent pregnancy, it is recommended to use other non-hormonal contraceptive methods;
• ethinyl estradiol/drospirenone. Darunavir Aurovitas may increase the risk of hyperkalemia caused by drospirenone.
• atorvastatin, pravastatin, rosuvastatin (medicines that lower cholesterol levels); there is a possibility of increased risk of muscle damage - the doctor will assess which cholesterol-lowering medicine is suitable in a given situation;
• clarithromycin (antibiotic);
• cyclosporine, everolimus, tacrolimus, sirolimus (medicines that weaken the immune system) due to the possibility of increased therapeutic and adverse effects of these medicines - the doctor may order additional tests;
• corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, and triamcinolone. These medicines are used to treat allergies, asthma, non-specific colitis, skin, eye, joint, and muscle inflammation, and other inflammatory conditions. They are usually taken orally, inhaled, injected, or applied to the skin. If alternative treatment cannot be used, these medicines can only be used after consulting a doctor and under close monitoring of corticosteroid side effects by the doctor;
• buprenorphine/naloxone (medicines used to treat opioid addiction);
• salmeterol (medicine used to treat asthma);
• artemether/lumefantrine (combined medicine used to treat malaria);
• dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (medicines used to treat cancer);
• sildenafil, tadalafil, vardenafil (medicines used to treat erectile dysfunction or pulmonary arterial hypertension);
• glecaprevir/pibrentasvir (medicine used to treat hepatitis C virus infection);
• fentanyl, oxycodone, tramadol (used to treat pain);
• fesoterodine, solifenacin (used to treat urological disorders).

The patient should inform their doctor about taking:

• edoxaban dabigatran, rivaroxaban, warfarin (medicines that reduce blood clotting);
• alfentanil (injection, strong and short-acting, pain reliever used in surgical procedures);
• digoxin (medicine used to treat certain heart diseases);
• clarithromycin (antibiotic);
• itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (antifungal medicines). Voriconazole can only be used after consulting a doctor;
• rifabutin (medicine used to treat bacterial infections);
• sildenafil, vardenafil, tadalafil (medicines used to treat erectile dysfunction or pulmonary arterial hypertension);
• amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (antidepressant and anxiolytic medicines);
• maraviroc (medicine used to treat HIV infection);
• methadone (medicine used to treat opioid addiction);
• carbamazepine, clonazepam (medicines used to prevent seizures or treat certain types of nerve pain);
• colchicine (medicine used to treat gout or familial Mediterranean fever);
• bosentan (medicine used to treat high blood pressure in the pulmonary circulation);
• buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam (injections), zolpidem (sedative and anxiolytic medicines);
• perphenazine, risperidone, tiordiazine (medicines used to treat mental disorders).

This is not a complete list of medicines. The patient should inform their doctor about allmedicines they are taking.

Taking Darunavir Aurovitas with food and drink

See section 3 "How to take Darunavir Aurovitas".

Pregnancy and breastfeeding

The patient should immediately inform their doctor about pregnancy or planned pregnancy. Pregnant women should not take Darunavir Aurovitas with ritonavir without special recommendation from their doctor. Pregnant women should not take Darunavir Aurovitas with cobicistat. Due to the possibility of side effects in breastfed children, women should not breastfeed while taking Darunavir Aurovitas. It is not recommended for HIV-infected women to breastfeed, as HIV can be transmitted to the child through breast milk. If the patient is breastfeeding or considering breastfeeding, they should consult their doctor as soon as possible.

Driving and operating machinery

The patient should not drive or operate machinery if taking Darunavir Aurovitas causes dizziness.

Darunavir Aurovitas contains propylene glycol

This medicine contains 83.34 mg of propylene glycol in each film-coated tablet. Before administering the medicine to a child under 4 weeks of age, the patient should consult their doctor or pharmacist, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to take Darunavir Aurovitas

The patient should always take this medicine exactly as prescribed by their doctor or pharmacist. In case of doubts, the patient should consult their doctor or pharmacist. The doctor will inform the patient about the dose of Darunavir Aurovitas to take. If the patient notices significant improvement, they should not stop taking Darunavir Aurovitas with ritonavir without consulting their doctor. After starting treatment, the patient should not change the dose, form of the medicine, or stop treatment without prior consultation with their doctor.

Dose for adults who have not previously taken antiretroviral medicines (determined by the doctor)

The patient requires a different dose of Darunavir Aurovitas, which cannot be administered using these tablets containing 600 mg of the medicine. Another strength of Darunavir Aurovitas is available.

Dose for adults who have previously taken antiretroviral medicines (determined by the doctor)

The dose is:

• 600 mg of Darunavir Aurovitas with 100 mg of ritonavir twice a day. OR
• 800 mg of Darunavir Aurovitas (1 tablet containing 800 mg of Darunavir Aurovitas) with 100 mg of ritonavir once a day. Darunavir Aurovitas 800 mg should only be used to create a dosing regimen of 800 mg once a day.

The doctor will discuss which dose is suitable for the patient.

Instructions for adults

• The patient should take Darunavir Aurovitas always with ritonavir. Darunavir Aurovitas does not work properly without ritonavir.
• The patient should take 600 mg of Darunavir Aurovitas in the morning with 100 mg of ritonavir.
• The patient should take 600 mg of Darunavir Aurovitas in the evening with 100 mg of ritonavir.
• The patient should take Darunavir Aurovitas with food. Darunavir Aurovitas does not work properly when taken without food. The type of food is not important.
• The patient should swallow the tablets with water or milk.

Dose for children aged 3 and over, weighing at least 15 kg, who have not previously taken antiretroviral medicines (determined by the doctor)

The doctor will choose the appropriate dose of the medicine based on the child's weight (see the table below). The dose should not exceed the recommended dose for adults, which is 800 mg of darunavir and 100 mg of ritonavir once a day. The doctor will inform the patient about the number of darunavir tablets and ritonavir (capsules, tablets, or oral solution) the child should take. Tablets with lower strengths are available to create an appropriate dosing regimen. With ritonavir oral solution: 80 mg/ml

Dose for children aged 3 and over, weighing at least 15 kg, who have previously taken antiretroviral medicines (determined by the doctor)

The doctor will choose the appropriate dose of the medicine based on the child's weight (see the table below). The doctor will assess whether once-daily or twice-daily dosing is suitable for the child. The dose should not exceed the recommended dose for adults, which is 600 mg for Darunavir Aurovitas and 100 mg of ritonavir twice a day, or 800 mg for Darunavir Aurovitas and 100 mg of ritonavir once a day. The doctor will inform the patient about the number of darunavir tablets and ritonavir (capsules, tablets, or oral solution) the child should take. Tablets with lower strengths are available to create an appropriate dosing regimen. The doctor will determine whether Darunavir Aurovitas tablets are suitable for the child. Twice-daily dosing For adolescents over 12 years of age, weighing at least 40 kg, the doctor will determine whether Darunavir Aurovitas 800 mg once a day can be used. This dose cannot be administered using these tablets containing 600 mg. Another strength of Darunavir Aurovitas is available. Once-daily dosing With ritonavir oral solution: 80 mg/ml

Instructions for taking Darunavir Aurovitas in children:

• The child must take Darunavir Aurovitas always in combination with ritonavir. Darunavir Aurovitas does not work properly without ritonavir.
• The child must take the appropriate dose of Darunavir Aurovitas and ritonavir twice a day or once a day. If Darunavir Aurovitas is prescribed twice a day, the child should take one dose in the morning and the second dose in the evening. The doctor will determine the appropriate dosing regimen for the child.
• The child must take Darunavir Aurovitas with food. Darunavir Aurovitas does not work properly when taken without food. The type of food is not important.
• The child must swallow the tablets with water or milk.

Child-resistant cap

The plastic bottle is provided with a child-resistant cap and should be opened as follows:

• Press the plastic cap down and turn it to the left.
• Remove the unscrewed cap.

Overdose

The patient should immediately contact their doctor, pharmacist, or nurse.

Missed dose

If the missed dose is noticed within 6 hours, the patient should take the missed tablets as soon as possible. Each dose of the medicine should be taken with ritonavir and food. If the missed dose is noticed after 6 hours, the patient should skip the missed dose and take the next dose at the usual time. The patient should not take a double dose to make up for the missed dose.

Vomiting after taking Darunavir Aurovitas and ritonavir

In case of vomiting within 4 hoursafter taking the medicine, the patient should take another dose of Darunavir Aurovitas and ritonavir as soon as possible with food. In case of vomiting more than 4 hoursafter taking the medicine, the patient should not take another dose of Darunavir Aurovitas and ritonavir until the next scheduled dose. If the patient is unsure about what to do in case of a missed dose or vomiting, they should contact their doctor.

Do not stop taking Darunavir Aurovitas without consulting a doctor

Antiretroviral medicines can improve the patient's condition, but even if they feel better, they should not stop taking Darunavir Aurovitas without prior consultation with their doctor. If the patient has any further doubts about taking this medicine, they should consult their doctor, pharmacist, or nurse.

4. Possible side effects

During HIV treatment, weight gain and increased levels of lipids and glucose in the blood may occur. This is partly related to the improvement in health and lifestyle, and in the case of lipid levels in the blood, sometimes to the use of HIV medicines themselves. The doctor will order tests to monitor these changes. Like all medicines, Darunavir Aurovitas can cause side effects, although not everybody gets them.

The patient should inform their doctor if they experience any of the following side effects

Liver problems have been reported, which have occasionally been severe. The doctor will perform blood tests before starting Darunavir Aurovitas. If the patient has chronic viral hepatitis B or C, the doctor should order blood tests more frequently, as there is an increased risk of liver problems. The patient should discuss with their doctor the symptoms of liver disorders, which may include: yellowing of the skin or eyes, dark urine (tea-colored), pale stools, nausea, vomiting, loss of appetite, or pain and discomfort below the right ribcage. Skin rash (occurring more frequently during simultaneous use of raltegravir), itching. The rash is usually mild or moderate. The rash can also be a symptom of a rare, severe disease. Therefore, the patient should discuss with their doctor if a rash occurs. The doctor will recommend appropriate treatment for the symptoms or decide to stop Darunavir Aurovitas. Other severe side effects have been: diabetes (often) and pancreatitis (not very often). Very common(may affect more than 1 in 10 people)

• diarrhea.

Common(may affect up to 1 in 10 people)

• vomiting, nausea, abdominal pain or bloating, indigestion, bloating;
• headache, fatigue, dizziness, drowsiness, numbness, tingling, or pain in the hands or feet, weakness, difficulty sleeping.

Uncommon(may affect up to 1 in 100 people)

• chest pain, changes in ECG, rapid heart rate;
• disorders or numbness of skin sensation, tingling, concentration disorders, memory loss, balance disorders;
• breathing difficulties, cough, nosebleeds, throat irritation;
• gastritis or oral inflammation, heartburn, gagging, 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 (most often around the mouth or eyes), rash, excessive sweating, night sweats, hair loss, acne, scaly skin, nail discoloration;
• muscle pain, muscle cramps or weakness, limb pain, osteoporosis;
• slowed thyroid function, which can be detected by blood tests;
• high blood pressure, sudden flushing of the face;
• redness or dryness of the eyes;
• fever, swelling of the lower limbs due to fluid retention, feeling unwell, irritability, pain;
• infection symptoms, herpes;
• erectile dysfunction, breast enlargement in men;
• sleep disorders, drowsiness, depression, anxiety, strange dreams, decreased libido.

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

• DRESS syndrome [severe rash, which may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophil count (a type of white blood cell), liver, kidney, or lung symptoms];
• heart attack, slow heart rate, palpitations;
• vision disorders;
• chills, malaise;
• feeling disoriented or lost, mood changes, restlessness;
• fainting, seizures, changes or loss of taste;
• mouth pain, bloody vomiting, mouth or lip inflammation, dry lips, coated tongue;
• common cold;
• diseased skin, dry skin;
• muscle stiffness or joint pain, joint pain with or without inflammation;
• blood cell count and biochemical test abnormalities. Changes can be observed in blood or urine test results. The doctor will provide detailed explanations. Examples of abnormalities include: increased count of a certain type of white blood cell;
• darunavir crystals in the kidneys causing kidney disease.

Side effects typical of HIV medicines from the same class as Darunavir Aurovitas include:

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

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl By reporting side effects, more information can be collected on the safety of the medicine. Side effects can also be reported to the marketing authorization holder.

5. How to store Darunavir Aurovitas

The medicine should be stored out of sight and reach of children. The patient should not use this medicine after the expiry date stated on the blister, label, carton, or bottle after: EXP. The expiry date refers to the last day of the month stated. There are no special precautions for storing the medicine. The patient should not use this medicine if they notice any changes in the appearance of the tablets. Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Darunavir Aurovitas contains

• The active substance of the medicine is darunavir (in the form of darunavir with propylene glycol).

Darunavir Aurovitas, 600 mg, film-coated tabletsEach film-coated tablet contains 600 mg of darunavir (in the form of darunavir with propylene glycol).

• Other ingredients are:

Tablet core: Microcrystalline cellulose (Type-101), hydroxypropyl cellulose, crospovidone (Type-B), colloidal silicon dioxide, magnesium stearate. Tablet coating: Ready-to-use coating material (white): Polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), and talc.

What Darunavir Aurovitas looks like and contents of the pack

Darunavir Aurovitas, 600 mg, film-coated tabletsWhite or almost white, oval, biconvex film-coated tablets with the inscription "D" on one side and "600" on the other side of the tablet. Darunavir Aurovitas is available in blisters and HDPE bottles with a PP child-resistant closure.

Pack sizes:

Blisters: 30, 50, 60, 90, 100, or 120 film-coated tablets. HDPE bottle: 60 film-coated tablets. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Aurovitas Pharma Polska Sp. z o.o. ul. Sokratesa 13D lokal 27 01-909 Warsaw e-mail: [email protected]

Manufacturer/Importer:

APL Swift Services (Malta) Ltd. HF26, Hal Far Industrial Estate, Hal Far Birzebbugia, BBG 3000 Malta Generics Farmacêutica, S.A. Rua João de Deus 19, Venda Nova 2700-487 Amadora Portugal Arrow Génériques 26 Avenue Tony Garnier 69007 Lyon France

This medicine is authorized in the Member States of the European Economic Area under the following names:

France: Darunavir Arrow 600 mg comprimé pelliculé Germany: Darunavir PUREN 600 mg Filmtabletten Netherlands: Darunavir Aurobindo 600 mg filmomhulde tabletten Poland: Darunavir Aurovitas Portugal: Darunavir Generis Romania: Darunavir Aurobindo 600 mg comprimate filmate Spain: Darunavir Aurovitas 600 mg comprimidos recubiertos con película EFG

Date of last revision of the leaflet: 09/2023